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Egyptian Journal of Medical Human Genetics
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MicroRNAs influence and longevity

Egyptian Journal of Medical Human Genetics volume 23, Article number: 105 (2022) Cite this article

Abstract

Background

MiRNAs play critical roles in the regulation of cellular function, life span, and the aging process. They can affect longevity positively and negatively through different aging pathways.

Main text

MiRNAs are a group of short non-coding RNAs that regulate gene expressions at post-transcriptional levels. The different types of alterations in miRNAs biogenesis, mRNA expressions, and activities of miRNA-protein complexes can affect the regulation of normal post-transcriptional gene process, which may lead to aging, age-related diseases, and an earlier death. It seems that the influence of deregulation of miRNAs on senescence and age-related diseases occurring by targeting aging molecular pathways can be used for diagnosis and prognosis of them. Therefore, the expression and function of miRNAs should be studied more accurately with new applicable and validated experimental tools. However, the current review wishes to highlight simply a connection among miRNAs, senescence and some age-related diseases.

Conclusion

Despite several research indicating the key roles of miRNAs in aging and longevity, further investigations are still needed to elucidate the essential roles of miRNAs in controlling mRNA regulation, cell proliferation, death and/or protection during stress and health problems. Besides, more research on miRNAs will help to identify new targets for alternative strategies regarding effectively screen, treat, and prevent diseases as well as make slow the aging process.

MicroRNAs (miRNAs)

MicroRNAs (miRNAs) are a large class of small non-coding RNAs functioning as the important regulators of a wide range of cellular processes [1] that have been identified firstly in C. elegans in 1993 [2,3,4]. They act as mediators that can regulate post-transcriptional gene expressions [5,6,7]; therefore, they are able to control cellular behavior, balance in biological processes, development, and diseases [7, 8] by modulating gene expression [1]. The post-transcriptional gene effect of miRNAs happens by base-pair binding on their related mRNAs targeting untranslated regions (UTRs) of genes and multiple sites within a single UTR [9]. Each miRNA can target multiple mRNAs, and one mRNA can be regulated by multiple miRNAs [10, 11]. MiRNAs have been found in plants, animals, bacteria and some viruses [12] by their gene expression profiling. In animal models, miRNAs contribute into genetic networks and metabolic pathways. It seems that miRNAs play critical roles in the occurrence of pathological conditions like neurodegeneration and cancer following the alterations in the expression of specific miRNAs in the brain and/or homeostasis in the body [6, 9].

Besides, some miRNAs are related to the regulation of senescence in a variety of human cells [8]. As it is shown in Table 1, cancer, cognition, and senescence can be associated with miRNAs [2, 6, 13,14,15,16,17]. Until now, more than 950 miRNAs in humans have been found [18]. It has been indicated that some of miRNAs are tissue- or cell-specific and some of them are house-keeping molecules. However, a relatively small number of miRNAs have probably key functions in order to regulate the human genome and affect post-transcriptional physiological process. It seems that they can influence differentiation and tumor suppression in cells, which may relate to some pathological processes such as carcinogenesis or senescence [10]. Thus, miRNAs have been suggested to be used as biomarkers to evaluate many diseases and aging [9], even though it is difficult to estimate miRNAs quantification due to their small size, low copy number, interference from other small RNAs, and contamination by degradation products of mRNAs or other RNA species [2].

Table 1 Showing the correlation of miRNAs with cancer, cognitive function and senescence
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Despite the presence of miRNAs in tissue cells, they can also be found in the body fluids and extracellular environments such as plasma, serum, urine, saliva, seminal fluid, ascites, pleural effusions, and cerebrospinal fluid [4, 19]. They are injected to the circulation in different ways. It can happen through a passive leakage following apoptosis, necrosis, inflammation, or an active secretion by exosomes/microvesicles, lipoproteins, and RNA–protein complex. Circulating miRNAs following packing into exosomes have been found specific to a tissue or a disease, which can indicate degree of tumor progression and stage of cancer. Several studies have also shown that the abnormality of specific circulating miRNAs can be associated with the manifestation, development, invasion, and metastasis of cancer [19]. However, miRNAs-related studies will increase our understanding regarding age-related gene regulation and improve miRNA-based biomarker development for an advance in RNA-based diagnosis and therapies [9]. Thus, the aging process and age-related problems and conditions can be better monitored. In addition, further studies will help to better identify specific miRNAs and their changes related to caloric restriction, aging and age-related diseases pathways.

Biogenesis of miRNA in animals

MiRNAs are a group of small non-coding RNA [8, 14, 20, 21] with approximately 21–24 nucleotide (nt) in length [3] that are widespread and probably regulate > 50% of the human genome [22]. They are produced from precursor molecules (pri-miRNAs), which are made through transcription by RNA polymerase II from independent genes or derived from introns after splicing. Pri-miRNAs are subsequently converted to pre-miRNAs by Drosha enzyme and exported to the cytoplasm. Dicer enzyme cleaves them to the mature approximately 20-bp miRNA 5p/3p pairs. One strand of this duplex will incorporate into the miRNA-inducing silencing complex (miRISC) [3, 23,24,25]. The process is summarized in Fig. 1.

Fig. 1
figure 1

Gene silencing procedure by miRNA

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The transcription of DNA coding for miRNAs and the related protein-coding genes occurs in a similar way. The mature miRNA directly interacts with a member of the Argonaute protein family, which results in the formation of the RNA-induced silencing complex (RISC). As a component of RISC, miRNAs direct the post-transcriptional repression. Thus, miRNAs show regulatory functions regarding gene expression and can play a central role in several cellular processes including cell growth, differentiation, proliferation, and apoptosis [18].

MiRNAs are potent negative regulators of gene expressions [8]. They regulate their target genes through either translational repression or mRNA degradation. Such functions happen via binding to the complementary regions of messenger transcripts [14] and targeting specific messenger RNAs (mRNAs) [21]. Each miRNA can target up to hundreds of mRNAs [8, 18, 26] and they are able to regulate the expression of more than 60% of protein-coding genes of the human genome [27]. The effect of miRNAs on the regulation of many human genes [28,29,30] indicates their critical roles in a variety of biological processes [8, 21].

MiRNAs are important epigenetic regulators [14] and many of them are also self-regulated epigenetically [8]. For instance, epigenetically transcriptional repression by miRNAs can be through DNA methylation and histone modifications in which to affect subsequently mostly CpG islands located in the promoter regions of genes and result in silencing of genes [31]. Moreover, miRNAs can also down-regulate mRNAs [26] by declining target mRNAs or the levels of translation into proteins [32]. The silence of target mRNAs is based on base-pairing recognition sites [8] and the interaction of miRNAs with the 3’ UTR of target mRNAs. Thus, mRNA degradation and/or translational repression result in gene silencing [4, 29, 33, 34].

However, miRNAs are known as major elements that can contribute into complex functional pathways, control cellular processes [35], and the regulation of biological functions [36] such as differentiation, proliferation, apoptosis, replicative senescence [21], development, and stress responses [35] in plants and animals (Table 2).

Table 2 Examples of miRNAs, targets and functions involved
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MiRNAs are in both intracellular and extracellular regions of the body [61]. Extracellular miRNAs can be used as biomarkers in which to evaluate a variety of diseases such as liver fibrosis and hepatocellular carcinoma. Besides, miRNAs play important roles in intercellular communication. Such miRNAs can be delivered to target cells, where they have hormone-like activities and may act as autocrine, paracrine, and/or endocrine regulators. It can modulate cellular activities [4] by changing the expression of proteins following the specific inhibition of mRNA targets in cell-free miRNAs, which may originate from one cell type and acquired by another cells or other cell types [11]. In addition, miRNAs, gene expression patterns, physiology, and homeostasis in cells are related to the effects of different factors such as stress [135].

Stress

Stress is caused by different stressors and is divided into acute, chronic and several forms. It can play an important role in daily life in which to threat an individual’s homeostasis, well-being, health, and/or survival. Stress is with a systemic physiological response such as inflammatory and cellular reactions, metabolic processes, and epigenetic regulation [18]. The occurrence of stress in cells may happen due to sudden or frequent changes in environmental factors. Stress can damage existing macromolecules in living cells such as proteins, mRNAs, DNA, and lipids, which in turn can increase the risk of death, metabolic imbalances [136], and chronic diseases [20] such as cognitive decline and cancer with advancing age [2].

The severity and duration of stress can affect cellular homeostasis in which to return to stable state or modify to a new state. However, responses to stress in the body can occur through several mechanisms [136] including induction of molecular chaperones [137, 138], rapid clearance of damaged macromolecules [139], activation of specific gene expressions, growth arrest [140], and cell death [20].

MiRNAs play critical roles in main cellular processes. Their identifying helps to understand the cellular stress responses and the occurrence of senescence associated with environmental changes [20]. Nowadays, there is a better understanding regarding the miRNAs involving in physiological reactions and reaction pathways as well as their regulatory roles. For instance, the alteration of miRNAs concentration such as miR-21 has been detected in some stress-related pathological conditions and diseases such as psychiatric diseases [18]. MiRNAs have shown regulatory role in the control of specific mRNA translation. It leads to a gene-specific control over protein translation, which reversibly and rapidly can regulate cellular landscape and also enables survival during periods of extreme stress with efficient utilization of ATP turnover [12]. Responses of cells to stresses are in the form of restoring or reprogramming of gene expression patterns mediated by miRNA functions, the amounts of miRNAs, the amount of mRNA targets, and the activity of miRNA-protein complexes. The levels of cells reactions can determine specificity, time, and concentration of genes related to products expressed at each stress situation [20].

Several studies indicate that miRNAs can have a major regulatory influence over a number of cellular processes in which to play essential roles in prolonged environmental stress survival [12]. For instance, several miRNAs are involved in the regulation of psychological stress effects on the genesis and maintenance of many diseases [18]. In addition, stress regulates both transcription and the biogenesis of miRNAs, which results in the accumulation of pre-miRNAs, the reduction of mature miRNAs, or facilitating the processing of some miRNAs. Such regulatory effect happens by mediating of some important factors such as SMADs, p53 and breast cancer 1 (BRCA1) protein [24]. Besides, psychological stress results in oxidative stress by induction of the sympathetic-adrenal-medullary (SAM) and later the hypothalamic–pituitary–adrenal (HPA) axis, which in turn can cause protein damages and induce specific cellular stress response pathways [18].

Such connections between several miRNAs and pathways in the body can probably explain the effect of stress on aging and age-related changes. For example, there is an association between the expression of some miRNAs (miR-217, miR-100, miR-34a, miR-199a, and miR-132) and different factors of sirtuin 1 (SIRT1) protein, chemokine production, and hypoxia-inducible factor-1 alpha (HIF-1α). It seems that such relation can affect hemostasis, normal growth, and maintenance of cells in the body [2]. The effect of miRNAs happens through recognizing partly complementary sequences in their own mRNA targets and inhibition of their expression by translational repression or degradation of the target mRNAs. As follows, it results in controlling protein synthesis in cells, which in turn plays an important role in regulating cell proliferation, development, and aging [135].

Aging

Aging is due to the accumulation of genetically and environmentally damages [8, 141, 142] accompanied with the unregulated repair systems of DNA [8]. The accumulations of cellular and molecular damages can cause aging and the functional decline of organs, which results in the increased risk of susceptibility to diseases and mortality [21, 143].

The nine hallmarks indicating aging are genomic instability, telomere reduction, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Besides, further studies show the presence of other hallmarks such as dysregulation of the extracellular matrix in aging, for example aging lung [144].

The senescent cell phenotype is under the combination effects of cell changes in morphology, behavior, structure, and functions. These changes occur due to alterations probably happening in gene expressions [145], protein secretions [146], and inducibility of apoptosis, which may increase in senescent fibroblasts [147] and decrease in endothelial cells [148].

The harmful altered senescent cells functions may accelerate senescence and/or loss of cells within tissues, resulting in the age-associated decline of body function and the increased rate of age-associated diseases [8]. It has been indicated that tissue micro-environment changes happening due to the age-related accumulation of senescent cells can promote age-related phenotypes, cancer [149,150,151], and neurological disorders [8]. However, changes in patterns of gene expression in cells following the effects of non-coding RNAs, particularly miRNAs can lead to different functions in senescent cells [8].

As it has been noted, miRNAs play key roles in the regulation of development, apoptosis and metabolism in the body; therefore, they regulate aging and processes responsible for life span determination in vertebrates [152]. Studies on aging in animal models have supported the major roles of miRNAs in modulating life span and the aging process [2]. Age‐related diseases can also be associated with changes in the expression of circulating miRNAs in the body fluids including serum and plasma. Such miRNAs are released during tissue injury or shed from the plasma membranes of various cell types. They are remarkably stable as well as resistant to heat, pH changes, long time storage, and repeated freeze and thaw cycles. Despite these findings, exact molecular pathways underlying aging are not yet well understood [8] and also little is known about the role of circulating miRNAs related to aging in humans [21].

Some of factors and pathways involved in the aging process are insulin/insulin-like growth factor (IGF)-1, phosphoinositide 3-kinase (PI3K), target of rapamycin (TOR), mitogen-activated protein kinase (MAPK), AMP-dependent protein kinase (AMPK), protein kinase C signaling pathway (PKC), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸb), transforming growth factor beta (TGF-β), WNT signaling pathway (wingless-related integration site), Notch signaling pathway, receptor tyrosine kinase (c-Kit), and H2A histone family member X (H2AX). It seems that miRNAs affect the aging process by targeting these mentioned pathways including insulin/IGF-1 pathway [2, 153]. For example, miR-100, miR-30a, and miR-34a contribute into TOR pathway (miR-100, miR-30a) and aging signaling pathway (miR-34a) as the common pathways affecting life span and aging. It has also been found that changes in miRNAs expression with age are opposite to mRNAs expression [2]. However, miRNAs have roles in the regulating aging and age-related specific phenotypes of tissue and cell type with up-regulation, down-regulation and targeting the genes involved in aging pathways during cellular senescence. Various miRNAs expressions involved in aging process can be associated with specificity of tissue and the tissue-specific functions of aging signaling pathways. Despite the up-regulation of some of miRNAs, such as miR-34 and miR-71 with aging, the vast majority of C. elegans miRNAs expression is down-regulated with aging. Such differences in their expression can be due to the globality or specificity of those miRNAs related to a tissue or differences found among plants, animals and viruses. Thus, it is important to find various factors that can actively affect up- or down-regulation of miRNAs with aging [153].

Recent studies have shown miRNAs effects on aging and age-related diseases. For instance, miRNAs can regulate all related aspects of cutaneous biogenesis, functionality, and aging. It has been found that some miRNAs, such as let-7, miR-17, and miR-34, were down-regulated in long-lived individuals. Such conserved miRNAs in humans, known as longevity-related miRNAs, presumably promote life span prolongation. Conversely, miRNA let-7, miR-17, and miR-34 are up-regulated in some age-related diseases such as cancers [48] and cardiovascular diseases [154]. Therefore, further investigations are needed to elucidate the relation between miRNAs and healthy aging.

Longevity

The solution of longevity and how to have a healthy aging is one of the principal challenges in biology and medicine. The improvement of lifestyle and reduction of environmental hazards can prevent diseases and increase health in general population. Besides, the genetic assessment of exceptional individuals can provide important biological insights regarding the basis of healthy aging and human longevity [155]. However, genetics in aging is investigated in which to evaluate life span, longevity, exceptional longevity, and healthy aging. Longevity is defined as a specific advanced age or older, which is often considered 100 years or above. Besides, healthy aging states a combination of old age and health. It indicates the absence of certain diseases, disabilities, and health problems such as cognitive impairment and mobility disorders in older people. It is probably because such people live much healthier [155]. Several studies indicated that life span can be associated with miRNAs expression changes [21]; therefore, the identification of miRNAs roles in the induction and maintenance of senescence [20] will clarify the mechanisms associated with age-related diseases [8]. Thus, miRNAs can be good biomarkers used in order to facilitate predicting individuals’ longevity [21] or treat premature aging and age-related diseases such as cognitive function in the future [156].

Different investigations have shown that changes in the expression of some miRNAs such as let-7, miR-17, and miR-34 have been involved in life span prolongation among long-lived individuals as well as age-related diseases such as cancers [48] and cardiovascular diseases [154]. Further studies suggested the expression profiles of miRNAs miR-211‐5p, miR-374a‐5p, miR-340‐3p, miR-376c‐3p, miR-5095, miR-1225‐3p [129], miR-146a, miR-21, and miR-483 can be used as useful biomarkers for predicting and evaluating aging and age-related diseases. It has been suggested that miRNAs with the decreased production of melatonin, the increased levels of inflammatory and ROS markers [51], and their association with mRNA and epigenetic factors can affect aging and age-related diseases [154] like neurodegenerative and cognitive disorders [157].

Cognition

Neurodegenerative diseases are progressive disorders of the nervous system [6]. There are many cognitive disorders such as Alzheimer, Parkinson, Schizophrenia, Huntington’s diseases, and Autism spectrum disorders [157]. Their pathogenesis is complex and involves the alterations of multiple basic cellular pathways and non-coding RNAs [6]. Non-coding RNAs like miRNAs [6] play key roles in a wide range of physiological processes in the body [158, 159]. For example, miRNAs can regulate the neuronal activity, which contributes into neurogenesis, neurodegeneration, and cognition [6, 160, 161]. Several studies showed that the genetic deletion of dicer and the disruption of miRNAs expressions can affect development, differentiation, morphogenesis, and signaling in neurons [158, 159].

Alzheimer disease is one of neurodegenerative diseases that is the most common cause of dementia. It is mostly related to the aging process [162]. Many cases of dementia have been progressed from mild cognitive impairment (MCI), which is a transitional phase between the cognitive changes of normal aging and senile dementia. It presents with memory or cognitive impairment without significant effect on daily living. The conversion rate of MCI to dementia is approximately 10–15% each year. As many people suffer from dementia; therefore, early and effective diagnosis and intervention of MCI can have a great effect to reduce or delay the progression of dementia [163, 164].

MiRNAs are one of the main regulators of homeostasis in neurons. Their dysregulation can result in pathological conditions in the brain; therefore, their regulatory functions may have great impact on neurodegenerative diseases [128]. Thus, using miRNAs especially multiple miRNAs and serum-based miRNA assays suggested as a method with a high sensitivity and specificity can be used in which to diagnose cognitive impairment [163]. For instance, miR-206 and miR-567 (hsa-mir-567) have been introduced as good biomarkers that can be used to evaluate MCI and the earliest stages of dementia due to their effects on the involved genes in the biological processes in neuronal cells and their crucial roles in the neuronal differentiation and brain development [128]. Many of miRNAs are specific for cells and tissues [165,166,167,168]. For example, axons, dendrites and synapses have their own miRNAs and various expressions of miRNAs in neurons in neurodegenerative diseases such as Alzheimer disease (AD) [14] are probably associated with dendritogenesis and axonal path [169].

AD damages are started in the hippocampus and spread progressively throughout the brain. Although pathological hallmarks of AD are intracellular neurofibrillary tangles, the abnormal deposition of tau protein, and the accumulation of extracellular plaques of β-Amyloid (Aβ) peptides [6], miRNAs network (Fig. 2), and changes such as alterations in miRNAs targeting APP (miR-29a, miR-29b) can also affect the process of this disease [54].

Fig. 2
figure 2

Alzheimer’s disease (AD) formation, longevity and miRNA

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Deregulation of miRNAs can lead to the Aβ-accumulation, which occurs probably due to the activation of several pathogenic cascades. MiRNAs play important roles in homeostasis and pathogenesis of diseases in the brain by targeting 3'-UTRs mRNA that are related to several important proteins such as amyloid-beta precursor protein (APP), transforming growth factor-beta-induced protein (TGFBI), Tripartite Motif Containing protein 2 (TRIM2), SIRT1, and BTB domain containing protein 3 (BTBD3) [6, 170]. For instance, miRNAs let-7 and miR-320 can affect cognition through DAF-12 signaling and insulin/IGF signaling (IIS) pathways, respectively [2].

Further studies showed that several miRNAs such as miR-34, miR-9, miR-124 [171], miR-137 [157], miR-132, and miR-212 play important roles in cognition and memory function. Besides, miRNAs reactions to the higher expression of SIRT1 (miR-132 and miR-212) [76], NF-kB protein complex (mir-125b and mir-146a), cell cycle proteins (mir-26b, mir-107, mir-125b, mir-107, and mir-34a) [53], mitochondrial fission, synaptic function, ATP generation, presynaptic calcium level (miR-484) [120], and the increased production of ROS (mir-210 and mir-146a) can lead to a possible explanation regarding the induction of aging and aging-related diseases. Such correlations may result in releasing factors including IL6, altered genes function such as p53 and/or altered Wnt signaling, which in turn may affect cell cycle control, apoptosis, DNA, and cellular senescence [53]. It is now necessary to obtain consistent knowledge about the role of miRNAs in the brain for the maintenance of cognitive function or the appearance of cognitive deficits. A variety of miRNAs and their combinatorial effects may mediate their roles in pathological disorders in the brain. Several studies suggest that miRNAs-based therapy can be an alternative in the future for diagnosis and treatment of diseases such as neurodegenerative diseases [157, 172] and cancers [19].

Cancer

MiRNAs are key molecular components of cells and play important roles in both normal and pathologic states in the body [173]; hence, changes in their expression can lead to human diseases such as cancers [61, 174, 175]. They act as regulators for controlling a wide range of biological functions including apoptosis, tumor cell proliferation, differentiation, cell cycle progression, invasion, and metastasis [61, 175, 176].

Cancers are a group of age-related diseases. The initiation and progression of cancers can be related to miRNAs deregulation in a cause-effect manner [8] as it has been indicated in Table 3. Thus, miRNAs can be good biomarkers [8] for diagnosis, prognosis, and prediction of tumors. Several investigations have identified specific miRNAs related to solid tumors and hematological malignancies [176, 178] and their actions and effects vary among cancers [61]. For instance, let-7 miRNA and miR-146 act in cancers through their corresponding pathways, namely RAS and KIT, respectively [82]. The effects of miRNAs on proliferation, invasion and cell survival in prostate and pancreatic cancers occur by targeting cyclin D1 (CCND1), Wnt family member 3A (WNT3A), and B-cell lymphoma 2 (BCL2). MiRNAs can regulate metabolism and energy production in oral cancers by targeting NAD-dependent deacetylase SIRT3 (miR-31). Tumor formation and metastasis in germ cell tumors and gastric cancer can be promoted by miRNAs, which happens through targeting tumor suppressor gene TOB1 (transducer of ERBB2. 1) (miR-371-3) [61]. More than half of miRNAs-related genes in cancers are located in either cancer-associated genomic regions leading to amplification, loss of heterozygosity, and breakpoints, or fragile sites [176, 178]. As shown in Fig. 3, miRNAs play important roles in cancers as oncogenes or tumor suppressors [35, 61]. The expressions of tissue-specific miRNAs may lead to malignant transformation changes as tumor formation and growth by repressing tumor suppressor genes or increasing oncogene expressions. Thus, miRNAs can be good biomarkers in order to evaluate cancers and their classifications [61]. Changes of miRNAs function as tumor suppressors may mediate suppression of normal cells functions, which may result in initiation of malignant transformation in cells. Alterations such as mutations, genomic deletions, epigenetic silencing, and miRNA processing alterations can change the function of miRNAs in the regulation of normal cell proliferations. The oncogenic role of miRNAs can also happen by triggering mRNAs, which may encode tumor suppressor proteins. Moreover, miRNAs affect the progression of tumor by influencing the inflammation system, the components of the innate immune system [175, 176], and the modulation of apoptosis [5].

Table 3 Examples of some miRNAs and indicating their roles in cancer
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Fig. 3
figure 3

Correlation of miRNA with tumor formation

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MiRNAs abnormal expression and their effects on inflammation and cell proliferation [179, 180] in cancers [35, 181, 182] can be due to various factors such as defect in miRNA biogenesis machinery, activity changes in drosha, dicer [183], and transcription factors [184], as well as epigenetic changes such as DNA methylation, and histone modifications (histone methylation, and histone acetylation) [35]; therefore, the controlling mechanism of miRNAs expression is almost same to protein-coding genes [182]. As miRNAs play important roles in the regulation of many cancer-related genes, identification of specific ones of them may act as powerful tools to aid in diagnosis and treatment of tumors [82].

One of miRNAs is MiR-34a that can be used as an important diagnostic and therapeutic miRNA in many cancers due to its general expression. MiRNAs can also be used in order to evaluate chemotherapy resistance in cancers such as lung cancer and breast cancer. Despite this, miRNAs expression among different cancer types varies in a wide range, as it has been shown for miR-155, miR-221, and miR-222 expression [61].

It has been noted that miRNAs can be associated with the risk of recurrence and the chance of relapse‐free survival in cancers. For example, the overexpression of miR‐210 in breast cancer is with a higher risk of relapsing and lower chance of survival [22]. On the other hand, some miRNAs such as miR-34 and miR-1 contribute into several biological processes of tumor cells, including differentiation, proliferation, and apoptosis through their down-regulation [185]. Besides, miRNAs can affect drug resistance of tumor cells, which may happen by targeting drug resistance-related genes and/or influencing genes that are related to cell proliferation, cell cycle, and apoptosis [103]. Thus, further research are required in order to understand the exact roles of miRNAs in the development [82], diagnosis, prognosis, treatment [5], and survival [13] of cancers.

Accordingly, gene therapy using miRNAs might be used in the future in which to block the progression of cancers [175] by inhibiting the overexpression of oncogenic miRNAs or replacing those that are effective on tumor suppressive genes [176]. As present cancer-related biomarkers are not specific for tissues and have poor early diagnosis and prognostic value; therefore, they cannot be used as targeted therapy for cancers. Thus, miRNAs sound to be good non-invasive cellular and molecular biomarkers that can be replaced in order to early diagnosis, prognosis, and treatment of cancers [19]. However, further studies are needed for increasing the related knowledge in order to cope with challenges such as miRNAs stability, delivery drug systems, and the control of target effects [176] in which to use the miRNA-based therapeutic approaches in cancers [19]. Despite several therapeutic miRNA delivery systems such as virus-based delivery, non-viral delivery (lipid-based, polymer-based, or chemical structures), and the emerged extracellular vesicle (EV)-based delivery, miRNA-based therapeutic approach is still one of the great challenges. However, it seems that further improvements in techniques such as the targeted-therapeutic miRNA delivery in miRNAs-therapy for the treatment of different cancers will happen in the future [61].

Limitations

However, there are some limitations that can restrict miRNA investigations. Identification of specific miRNAs and their own targets in different diseases such as cancers and dementia is difficult and it limits the use of the miRNA-based therapeutic approaches. MiRNA and the related targeted mRNA must express at the same time in which to change gene expression, protein and biological function. It would be even more complex, when a single miRNA can target hundreds of mRNAs and vice versa. Therefore, it is crucial to identify and validate miRNA/mRNA target pairs and verify their interactions. In addition, technical limitations and delivery problems should be considered as extra factors that can confine such related studies.

Conclusion

This review highlights some relationships among miRNAs, senescence, cancer, and cognitive decline. Different investigations have shown that the actions and biological roles of miRNAs vary in various biological conditions. As noted in the review, further studies are needed to understand better the roles of miRNAs in the development and death of cells in aging and age-related diseases. Such new investigations can help to identify new targets for alternative strategies in order to treat or prevent diseases such as cancers and cognitive decline. The discovery of specific miRNAs will lead to find new biomarkers for screening and diagnosis of diseases as well as exploring of new therapeutic applications in numerous diseases in the future.

Availability of data and materials

Not applicable.

Abbreviations

miRNAs:

MicroRNAs

UTRs:

MRNAs targeting untranslated regions

miRISC:

MiRNA-inducing silencing complex

RISC:

RNA-induced silencing complex

mRNAs:

Messenger RNAs

ATP:

Adenosine Triphosphate

ROS:

Reactive oxygen species

SAM:

Sympathetic-adrenal-medullary

HPA:

Hypothalamic–pituitary–adrenal

HIF-1α:

Hypoxia-inducible factor-1 alpha

IGF-1:

Insulin/insulin-like growth factor

PI3K:

Phosphoinositide 3-kinase

TOR:

Target of rapamycin

MAPK:

Mitogen-activated protein kinase

AMPK:

AMP-dependent protein kinase

PKC:

Protein kinase C signaling pathway

NF-ĸb:

Nuclear factor kappa-light-chain-enhancer of activated B cells

TGF-β:

Transforming growth factor beta

wingless-related integration site:

WNT signaling pathway

c-Kit:

Notch signaling pathway, receptor tyrosine kinase

H2AX:

H2A histone family member X

MCI:

Mild cognitive impairment

Aβ peptides:

β-Amyloid

APP:

Amyloid-beta precursor protein

TGFBI:

Transforming growth factor-beta-induced protein

TRIM2:

Tripartite Motif Containing protein 2

BTBD3:

BTB domain containing protein 3

CCND1:

Cyclin D1

WNT3A:

Wnt family member 3A

BCL2:

B-cell lymphoma 2

References

  1. Van Rooij E (2011) The art of microRNA research. Circ Res 108(2):219–234

    Article  PubMed  Google Scholar 

  2. Jung HJ, Suh Y (2012) MicroRNA in aging: from discovery to biology. Curr Genomics 13(7):548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lou S, Sun T, Li H, Hu Z (2018) Mechanisms of microRNA-mediated gene regulation in unicellular model alga Chlamydomonas reinhardtii. Biotechnol Biofuels 11(1):1–12

    Article  Google Scholar 

  4. O’Brien J, Hayder H, Zayed Y, Peng C (2018) Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 9:402

    Article  CAS  Google Scholar 

  5. Ahmad J, Hasnain SE, Siddiqui MA, Ahamed M, Musarrat J, Al-Khedhairy AA (2013) MicroRNA in carcinogenesis & cancer diagnostics: A new paradigm. Indian J Med Res 137(4):680

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bicchi I, Morena F, Montesano S, Polidoro M, Martino S (2013) MicroRNAs and molecular mechanisms of neurodegeneration. Genes 4(2):244–263

    Article  PubMed  PubMed Central  Google Scholar 

  7. Alberti C, Cochella L (2017) A framework for understanding the roles of miRNAs in animal development. Development 144(14):2548–2559

    Article  CAS  PubMed  Google Scholar 

  8. Schraml E, Grillari J (2012) From cellular senescence to age-associated diseases: the miRNA connection. Longevity Healthspan 1(10):256

    Google Scholar 

  9. Fehlmann T, Lehallier B, Schaum N, Hahn O, Kahraman M, Li Y et al (2020) Common diseases alter the physiological age-related blood microRNA profile. Nat Commun 11(1):1–14

    Article  Google Scholar 

  10. ElSharawy A, Keller A, Flachsbart F, Wendschlag A, Jacobs G, Kefer N et al (2012) Genome-wide miRNA signatures of human longevity. Aging Cell 11(4):607–616

    Article  CAS  PubMed  Google Scholar 

  11. Umansky S (2018) Aging and aging-associated diseases: a microRNA-based endocrine regulation hypothesis. Aging (Albany NY) 10(10):2557

    Article  CAS  Google Scholar 

  12. Biggar KK, Storey KB (2018) Functional impact of microRNA regulation in models of extreme stress adaptation. J Mol Cell Biol 10(2):93–101

    Article  CAS  PubMed  Google Scholar 

  13. Almeida MI, Reis RM, Calin GA (2011) MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res Fundam Mol Mech Mutagen 717(1):1–8

    Article  CAS  Google Scholar 

  14. Sheinerman KS, Tsivinsky VG, Crawford F, Mullan MJ, Abdullah L, Umansky SR (2012) Plasma microRNA biomarkers for detection of mild cognitive impairment. Aging (Albany NY) 4(9):590

    Article  CAS  Google Scholar 

  15. Ai J, Sun L-H, Che H, Zhang R, Zhang T-Z, Wu W-C et al (2013) MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats. J Neurosci 33(9):3989–4001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Holohan KN, Lahiri DK, Schneider BP, Foroud TM, Saykin AJ (2013) Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways. Front Genet 3:323

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nidadavolu LS, Niedernhofer LJ, Khan SA (2013) Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxic stress. Aging (Albany NY) 5(6):460

    Article  CAS  Google Scholar 

  18. Wiegand C, Savelsbergh A, Heusser P (2017) MicroRNAs in psychological stress reactions and their use as stress-associated biomarkers, especially in human saliva. Biomed Hub 2(3):1–15

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cui M, Wang H, Yao X, Zhang D, Xie Y, Cui R et al (2019) Circulating microRNAs in cancer: potential and challenge. Front Genet 10:626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Leung AK, Sharp PA (2010) MicroRNA functions in stress responses. Mol Cell 40(2):205–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hooten NN, Fitzpatrick M, Wood WH 3rd, De S, Ejiogu N, Zhang Y et al (2013) Age-related changes in microRNA levels in serum. Aging (Albany NY) 5(10):725

    Article  Google Scholar 

  22. Tan W, Liu B, Qu S, Liang G, Luo W, Gong C (2018) MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett 15(3):2735–2742

    PubMed  Google Scholar 

  23. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610

    Article  CAS  PubMed  Google Scholar 

  24. Olejniczak M, Kotowska-Zimmer A, Krzyzosiak W (2018) Stress-induced changes in miRNA biogenesis and functioning. Cell Mol Life Sci 75(2):177–191

    Article  CAS  PubMed  Google Scholar 

  25. Allen L, Dwivedi Y (2020) MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior. Mol Psychiatry 25(2):308–320

    Article  CAS  PubMed  Google Scholar 

  26. Faraonio R, Salerno P, Passaro F, Sedia C, Iaccio A, Bellelli R et al (2011) A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts. Cell Death Differ 19(4):713–721

    Article  PubMed  PubMed Central  Google Scholar 

  27. Catalanotto C, Cogoni C, Zardo G (2016) MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci 17(10):1712

    Article  PubMed Central  Google Scholar 

  28. Kato M, Slack FJ (2008) microRNAs: small molecules with big roles-C. Elegans to human cancer. Biol Cell 100(2):71–81

    Article  CAS  PubMed  Google Scholar 

  29. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139

    Article  CAS  PubMed  Google Scholar 

  31. Morales S, Monzo M, Navarro A (2017) Epigenetic regulation mechanisms of microRNA expression. Biomol Concepts 8(5–6):203–212

    Article  CAS  PubMed  Google Scholar 

  32. Shin K-H, Pucar A, Kim RH, Bae SD, Chen W, Kang MK et al (2011) Identification of senescence-inducing microRNAs in normal human keratinocytes. Int J Oncol 39(5):1205

    CAS  PubMed  Google Scholar 

  33. Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell 132(1):9–14

    Article  CAS  PubMed  Google Scholar 

  34. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang J, Sen S (2011) MicroRNA functional network in pancreatic cancer: from biology to biomarkers of disease. J Biosci 36(3):481–491

    Article  CAS  PubMed  Google Scholar 

  36. Wang Z, Yao H, Lin S, Zhu X, Shen Z, Lu G et al (2013) Transcriptional and epigenetic regulation of human microRNAs. Cancer Lett 331(1):1–10

    Article  CAS  PubMed  Google Scholar 

  37. Mitchelson KR, Qin W-Y (2015) Roles of the canonical myomiRs miR-1,-133 and-206 in cell development and disease. World J Biol Chem 6(3):162

    Article  PubMed  PubMed Central  Google Scholar 

  38. Liu C, Zhang S, Wang Q, Zhang X (2017) Tumor suppressor miR-1 inhibits tumor growth and metastasis by simultaneously targeting multiple genes. Oncotarget 8(26):42043

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ma J-C, Duan M-J, Sun L-L, Yan M-L, Liu T, Wang Q et al (2015) Cardiac over-expression of microRNA-1 induces impairment of cognition in mice. Neuroscience 299:66–78

    Article  CAS  PubMed  Google Scholar 

  40. Lin X, Zhan J-K, Wang Y-J, Tan P, Chen Y-Y, Deng H-Q et al (2016) Function, role, and clinical application of microRNAs in vascular aging. BioMed Res Int 2016:145

    Article  Google Scholar 

  41. Jia B, Dao J, Han J, Huang Z, Sun X, Zheng X et al (2021) LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway. Cancer Cell Int 21(1):1–16

    Article  CAS  Google Scholar 

  42. Chirshev E, Oberg KC, Ioffe YJ, Unternaehrer JJ (2019) Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med 8(1):1–14

    Article  Google Scholar 

  43. Derkow K, Rössling R, Schipke C, Krüger C, Bauer J, Fähling M et al (2018) Distinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer’s disease. PLoS ONE 13(7):e0200602

    Article  PubMed  PubMed Central  Google Scholar 

  44. Suh N (2018) MicroRNA controls of cellular senescence. BMB Rep 51(10):493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen X, Yang F, Zhang T, Wang W, Xi W, Li Y et al (2019) MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma. J Exp Clin Cancer Res 38(1):1–16

    Article  Google Scholar 

  46. Basavaraju M, De Lencastre A (2016) Alzheimer’s disease: presence and role of microRNAs. Biomol Concepts 7(4):241–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. An X, Sarmiento C, Tan T, Zhu H (2017) Regulation of multidrug resistance by microRNAs in anti-cancer therapy. Acta Pharm Sin B 7(1):38–51

    Article  PubMed  Google Scholar 

  48. Gerasymchuk M, Cherkasova V, Kovalchuk O, Kovalchuk I (2020) The role of microRNAs in organismal and skin aging. Int J Mol Sci 21(15):5281

    Article  CAS  PubMed Central  Google Scholar 

  49. Kou X, Chen D, Chen N (2020) The regulation of microRNAs in Alzheimer’s disease. Front Neurol 11:154

    Article  Google Scholar 

  50. Gong B, Liu W-W, Nie W-J, Li D-F, Xie Z-J, Liu C et al (2015) MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways. World J Gastroenterol WJG 21(5):1488

    Article  CAS  PubMed  Google Scholar 

  51. Rusanova I, Diaz-Casado ME, Fernández-Ortiz M, Aranda-Martínez P, Guerra-Librero A, García-García FJ et al (2018) Analysis of plasma MicroRNAs as predictors and biomarkers of aging and frailty in humans. Oxid Med Cell Long 2018:1547

    Google Scholar 

  52. Amakiri N, Kubosumi A, Tran J, Reddy PH (2019) Amyloid beta and microRNAs in Alzheimer’s disease. Front Neurosci 13:430

    Article  PubMed  PubMed Central  Google Scholar 

  53. Swarbrick S, Wragg N, Ghosh S, Stolzing A (2019) Systematic review of miRNA as biomarkers in Alzheimer’s disease. Mol Neurobiol 56(9):6156–6167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hébert SS, Horré K, Nicolaï L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN et al (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/β-secretase expression. Proc Natl Acad Sci 105(17):6415–6420

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wang Y, Chang W, Chang W, Chang X, Zhai S, Pan G et al (2018) MicroRNA-376c-3p facilitates human hepatocellular carcinoma progression via repressing AT-rich interaction domain 2. J Cancer 9(22):4187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhao W, Cheng L, Quek C, Bellingham SA, Hill AF (2019) Novel miR-29b target regulation patterns are revealed in two different cell lines. Sci Rep 9(1):1–17

    Article  Google Scholar 

  57. Xia T, Dong S, Tian J (2020) miR-29b promotes the osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue via the PTEN/AKT/β-catenin signaling pathway. Int J Mol Med 46(2):709–717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Tabak S, Schreiber-Avissar S, Beit-Yannai E (2021) Crosstalk between MicroRNA and oxidative stress in primary open-angle glaucoma. Int J Mol Sci 22(5):2421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jiang L-H, Zhang H-D, Tang J-H (2018) MiR-30a: a novel biomarker and potential therapeutic target for cancer. J Oncol 2018:894

    Article  Google Scholar 

  60. Rege SD, Geetha T, Pondugula SR, Zizza CA, Wernette CM, Ramesh Babu J (2013) Noncoding RNAs in neurodegenerative diseases. Int Scholarly Res Not 2013:256

    Google Scholar 

  61. Forterre A, Komuro H, Aminova S, Harada M (2020) A comprehensive review of cancer MicroRNA therapeutic delivery strategies. Cancers 12(7):1852

    Article  CAS  PubMed Central  Google Scholar 

  62. Yu T, Ma P, Wu D, Shu Y, Gao W (2018) Functions and mechanisms of microRNA-31 in human cancers. Biomed Pharmacother 108:1162–1169

    Article  CAS  PubMed  Google Scholar 

  63. Barros-Viegas AT, Carmona V, Ferreiro E, Guedes J, Cardoso AM, Cunha P et al (2020) miRNA-31 improves cognition and abolishes amyloid-β pathology by targeting APP and BACE1 in an animal model of Alzheimer’s disease. Mol Therapy Nucleic Acids 19:1219–1236

    Article  CAS  PubMed  Google Scholar 

  64. Cho J-H, Dimri M, Dimri GP (2015) MicroRNA-31 is a transcriptional target of histone deacetylase inhibitors and a regulator of cellular senescence. J Biol Chem 290(16):10555–10567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rokavec M, Li H, Jiang L, Hermeking H (2014) The p53/miR-34 axis in development and disease. J Mol Cell Biol 6(3):214–230

    Article  CAS  PubMed  Google Scholar 

  66. Qiang J, Zhu X-W, He J, Tao Y-F, Bao J-W, Zhu J-H et al (2020) miR-34a regulates the activity of HIF-1a and P53 signaling pathways by promoting GLUT1 in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) under hypoxia stress. Front Physiol 11:1245

    Article  Google Scholar 

  67. Ruediger C, Shapira M (2019) mir-71 mediates age-dependent opposing contributions of the stress activated kinase KGB-1 in Caenorhabditis elegans. bioRxiv. 835355

  68. Zhang X, Zabinsky R, Teng Y, Cui M, Han M (2011) microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause. Proc Natl Acad Sci 108(44):17997–18002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Finger F, Ottens F, Springhorn A, Drexel T, Proksch L, Metz S et al (2019) Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signalling. Nat Metab 1(3):350–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Blick C, Ramachandran A, Wigfield S, McCormick R, Jubb A, Buffa F et al (2013) Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer. Br J Cancer 109(1):50–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kumar S, Reddy PH (2016) Are circulating microRNAs peripheral biomarkers for Alzheimer’s disease? Biochim Biophys Acta BBA Mol Basis Dis 1862(9):1617–1627

    Article  CAS  Google Scholar 

  72. Zhang Z-C, Liu J-X, Shao Z-W, Pu F-F, Wang B-C, Wu Q et al (2017) In vitro effect of microRNA-107 targeting Dkk-1 by regulation of Wnt/β-catenin signaling pathway in osteosarcoma. Medicine 96(27):584

    Article  Google Scholar 

  73. Jiao S, Liu Y, Yao Y, Teng J (2017) miR-124 promotes proliferation and differentiation of neuronal stem cells through inactivating Notch pathway. Cell Biosci 7(1):1–12

    Article  Google Scholar 

  74. Sun H-Y, Huang Y-H, Yu Z-H, Qin Q-W (2020) MiR-124 involvement of apoptosis, immunity and regulator of diseases. Afr J Biotech 19(3):142–147

    Article  Google Scholar 

  75. Wang Y, Zeng G, Jiang Y (2020) The emerging roles of miR-125b in cancers. Cancer Manag Res 12:1079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hadar A, Milanesi E, Walczak M, Puzianowska-Kuźnicka M, Kuźnicki J, Squassina A et al (2018) SIRT1, miR-132 and miR-212 link human longevity to Alzheimer’s disease. Sci Rep 8(1):1–10

    Article  CAS  Google Scholar 

  77. El Fatimy R, Li S, Chen Z, Mushannen T, Gongala S, Wei Z et al (2018) MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways. Acta Neuropathol 136(4):537–555

    Article  PubMed  PubMed Central  Google Scholar 

  78. Mziaut H, Henniger G, Ganss K, Hempel S, Wolk S, McChord J et al (2017) Mir-132 controls beta cell proliferation and survival in mouse model

  79. You J, Li Y, Fang N, Liu B, Zu L, Chang R et al (2014) MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2. PLoS ONE 9(3):e91827

    Article  PubMed  PubMed Central  Google Scholar 

  80. Mahmoudi E, Cairns M (2017) MiR-137: an important player in neural development and neoplastic transformation. Mol Psychiatry 22(1):44–55

    Article  CAS  PubMed  Google Scholar 

  81. Tian R, Wu B, Fu C, Guo K (2020) miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke. Aging (Albany NY) 12(11):10873

    Article  CAS  Google Scholar 

  82. Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM (2006) MicroRNA expression and function in cancer. Trends Mol Med 12(12):580–587

    Article  CAS  PubMed  Google Scholar 

  83. McGarty TP (2014) Notch pathway, MiR‐146a and melanoma

  84. Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D et al (2013) Micro RNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med 5(7):1017–1034

    Article  PubMed  Google Scholar 

  85. Ye E-A, Steinle JJ (2016) miR-146a attenuates inflammatory pathways mediated by TLR4/NF-κB and TNFα to protect primary human retinal microvascular endothelial cells grown in high glucose. Mediat Inflam 2016:1487

    Article  Google Scholar 

  86. Wani JA, Majid S, Khan A, Arafah A, Ahmad A, Jan BL et al (2021) Clinico-pathological importance of miR-146a in lung cancer. Diagnostics 11(2):274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Czyzyk-Krzeska M, Zhang X (2014) MiR-155 at the heart of oncogenic pathways. Oncogene 33(6):677–678

    Article  CAS  PubMed  Google Scholar 

  88. Mashima R (2015) Physiological roles of miR-155. Immunology 145(3):323–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Han B, Wang S, Zhao H (2020) MicroRNA-21 and microRNA-155 promote the progression of Burkitt’s lymphoma by the PI3K/AKT signaling pathway. Int J Clin Exp Pathol 13(1):89

    PubMed  PubMed Central  Google Scholar 

  90. Readhead B, Haure-Mirande J-V, Mastroeni D, Audrain M, Fanutza T, Kim SH et al (2020) miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer’s disease. Acta Neuropathol 140(3):295–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Soliman B, Salem A, Ghazy M, Abu-Shahba N, El Hefnawi M (2018) Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma. Tumor Biol 40(5):1010428318773675

    Article  Google Scholar 

  92. Wu L, Xi Y, Kong Q (2020) Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α. Artif Cells Nanomed Biotechnol 48(1):506–514

    Article  CAS  PubMed  Google Scholar 

  93. Wang Q, Ye B, Wang P, Yao F, Zhang C, Yu G (2019) Overview of microRNA-199a regulation in cancer. Cancer Manag Res 11:10327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Yamakuchi M (2012) Endothelial senescence and microRNA. Biomol Concepts 3(3):213–223

    Article  CAS  PubMed  Google Scholar 

  95. Deng M, Qin Y, Chen X, Wang Q, Wang J (2019) MiR-206 inhibits proliferation, migration, and invasion of gastric cancer cells by targeting the MUC1 gene. Onco Targets Ther 12:849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Liu X, Yang Z, Meng Q, Chen Y, Shao L, Li J et al (2020) Downregulation of microRNA-206 alleviates the sublethal oxidative stress-induced premature senescence and dysfunction in mesenchymal stem cells via targeting alpl. Oxid Med Cell Longev 2020:1236

    Google Scholar 

  97. Bavelloni A, Ramazzotti G, Poli A, Piazzi M, Focaccia E, Blalock W et al (2017) MiRNA-210: a current overview. Anticancer Res 37(12):6511–6521

    CAS  PubMed  Google Scholar 

  98. Bu H, Wedel S, Cavinato M, Jansen-Dürr P (2017) MicroRNA regulation of oxidative stress-induced cellular senescence. Oxid Med Cell Longev 2017:748

    Article  Google Scholar 

  99. Fan C, Wu Q, Ye X, Luo H, Yan D, Xiong Y et al (2016) Role of miR-211 in neuronal differentiation and viability: implications to pathogenesis of Alzheimer’s disease. Front Aging Neurosci 8:166

    Article  PubMed  PubMed Central  Google Scholar 

  100. Chen W, Song J, Bian H, Yang X, Xie X, Zhu Q et al (2020) The functions and targets of miR-212 as a potential biomarker of cancer diagnosis and therapy. J Cell Mol Med 24(4):2392–2401

    Article  PubMed  PubMed Central  Google Scholar 

  101. Ramalinga M, Roy A, Srivastava A, Bhattarai A, Harish V, Suy S et al (2015) MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence. Oncotarget 6(33):34446

    Article  PubMed  PubMed Central  Google Scholar 

  102. Zhang N, Lu C, Chen L (2016) miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer. Oncol Lett 12(6):4589–4597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Si W, Shen J, Zheng H, Fan W (2019) The role and mechanisms of action of microRNAs in cancer drug resistance. Clin Epigenet 11(1):1–24

    Article  Google Scholar 

  104. Song Q, An Q, Niu B, Lu X, Zhang N, Cao X (2019) Role of miR-221/222 in tumor development and the underlying mechanism. J Oncol 2019:526

    Article  Google Scholar 

  105. Manzine PR, Pelucchi S, Horst MA, Vale FA, Pavarini SC, Audano M et al (2018) microRNA 221 Targets ADAM10 mRNA and is downregulated in Alzheimer’s disease. J Alzheimers Dis 61(1):113–123

    Article  CAS  PubMed  Google Scholar 

  106. Zeng Q, Zou L, Qian L, Zhou F, Nie H, Yu S et al (2017) Expression of microRNA-222 in serum of patients with Alzheimer’s disease. Mol Med Rep 16(4):5575–5579

    Article  CAS  PubMed  Google Scholar 

  107. Wan C, Wen J, Liang X, Xie Q, Wu W, Wu M et al (2021) Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes. Sci Rep 11(1):1–11

    Article  Google Scholar 

  108. Luo L, Yang R, Zhao S, Chen Y, Hong S, Wang K et al (2018) Decreased miR-320 expression is associated with breast cancer progression, cell migration, and invasiveness via targeting Aquaporin 1. Acta Biochim Biophys Sin 50(5):473–480

    Article  CAS  PubMed  Google Scholar 

  109. Hatse S, Brouwers B, Dalmasso B, Laenen A, Kenis C, Schöffski P et al (2014) Circulating MicroRNAs as easy-to-measure aging biomarkers in older breast cancer patients: correlation with chronological age but not with fitness/frailty status. PLoS ONE 9(10):e110644

    Article  PubMed  PubMed Central  Google Scholar 

  110. Martinez-Gutierrez AD, Cantú de León D, Millan-Catalan O, Coronel-Hernandez J, Campos-Parra AD, Porras-Reyes F et al (2020) Identification of miRNA master regulators in breast cancer. Cells 9(7):1610

    Article  CAS  PubMed Central  Google Scholar 

  111. Huang Z, Xu Y, Wan M, Zeng X, Wu J (2021) miR-340: a multifunctional role in human malignant diseases. Int J Biol Sci 17(1):236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Sahu N, Stephan J-P, Cruz DD, Merchant M, Haley B, Bourgon R et al (2016) Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs. Nat Commun 7(1):1–10

    Article  Google Scholar 

  113. Ji R, Zhang X, Gu H, Ma J, Wen X, Zhou J et al (2019) miR-374a-5p: A new target for diagnosis and drug resistance therapy in gastric cancer. Mol Therapy-Nucleic Acids 18:320–331

    Article  CAS  Google Scholar 

  114. Bian H, Zhou Y, Zhou D, Zhang Y, Shang D, Qi J (2019) The latest progress on miR-374 and its functional implications in physiological and pathological processes. J Cell Mol Med 23(5):3063–3076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Unterbruner K, Matthes F, Schilling J, Nalavade R, Weber S, Winter J et al (2018) MicroRNAs miR-19, miR-340, miR-374 and miR-542 regulate MID1 protein expression. PLoS ONE 13(1):e0190437

    Article  PubMed  PubMed Central  Google Scholar 

  116. Ekowati AL, Pramono ZAD, Soeselo DA, Budiyanto A, Astuti I, Mubarika S (2019) hsa-miR-376c-3p in the circulating plasma is upregulated in the elderly javanese male when compared to their younger counterparts. Indonesian Biomed J 11(3):304–313

    Article  Google Scholar 

  117. Cao X, Zhang J, Apaer S, Yao G, Li T (2021) microRNA-19a-3p and microRNA-376c-3p promote hepatocellular carcinoma progression through SOX6-mediated Wnt/β-catenin signaling pathway. Int J Gener Med 14:89

    Article  CAS  Google Scholar 

  118. Wang L-L, Min L, Guo Q-D, Zhang J-X, Jiang H-L, Shao S et al (2017) Profiling microRNA from brain by microarray in a transgenic mouse model of Alzheimer’s disease. BioMed Res Int 2017:1254

    Google Scholar 

  119. Zhou W, Yang W, Ma J, Zhang H, Li Z, Zhang L et al (2018) Role of miR-483 in digestive tract cancers: from basic research to clinical value. J Cancer 9(2):407

    Article  PubMed  PubMed Central  Google Scholar 

  120. Wingo TS, Yang J, Fan W, Canon SM, Gerasimov ES, Lori A et al (2020) Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia. NPJ Genom Med 5(1):1–8

    Article  Google Scholar 

  121. Holubekova V, Kolkova Z, Grendar M, Brany D, Dvorska D, Stastny I et al (2020) Pathway analysis of selected circulating miRNAs in plasma of breast cancer patients: a preliminary study. Int J Mol Sci 21(19):7288

    Article  CAS  PubMed Central  Google Scholar 

  122. Lee D, Tang W, Dorsey TH, Ambs S (2020) miR-484 is associated with disease recurrence and promotes migration in prostate cancer. Biosci Rep 40(5):124

    Article  Google Scholar 

  123. Yu C, Tian F, Liu J, Su M, Wu M, Zhu X et al (2019) Circular RNA cMras inhibits lung adenocarcinoma progression via modulating miR-567/PTPRG regulatory pathway. Cell Prolif 52(3):e12610

    Article  PubMed  PubMed Central  Google Scholar 

  124. Bertoli G, Cava C, Diceglie C, Martelli C, Rizzo G, Piccotti F et al (2017) MicroRNA-567 dysregulation contributes to carcinogenesis of breast cancer, targeting tumor cell proliferation, and migration. Breast Cancer Res Treat 161(3):605–616

    Article  CAS  PubMed  Google Scholar 

  125. Han M, Hu J, Lu P, Cao H, Yu C, Li X et al (2020) Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer. Cell Death Dis 11(1):1–15

    Article  Google Scholar 

  126. Elkady MA, Doghish AS, Elshafei A, Elshafey MM (2021) MicroRNA-567 inhibits cell proliferation and induces cell apoptosis in A549 NSCLC cells by regulating cyclin-dependent kinase 8. Saudi J Biol Sci 28(4):2581–2590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhang F, Li K, Yao X, Wang H, Li W, Wu J et al (2019) A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer. EBioMedicine 44:311–321

    Article  PubMed  PubMed Central  Google Scholar 

  128. De Felice B, Montanino C, Oliva M, Bonavita S, Di Onofrio V, Coppola C (2020) MicroRNA expression signature in mild cognitive impairment due to Alzheimer’s disease. Mol Neurobiol 57(11):4408–4416

    Article  PubMed  PubMed Central  Google Scholar 

  129. Smith-Vikos T, Liu Z, Parsons C, Gorospe M, Ferrucci L, Gill TM et al (2016) A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA). Aging (Albany NY) 8(11):2971

    Article  CAS  Google Scholar 

  130. Urh K, Žlajpah M, Zidar N, Boštjančič E (2021) Identification and validation of new cancer stem cell-related genes and their regulatory microRNAs in colorectal cancerogenesis. Biomedicines 9(2):179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Gong F, Hou G, Liu H, Zhang M (2015) Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of mTOR/p70S6K pathway in esophageal squamous cell carcinoma. Med Oncol 32(2):25

    Article  Google Scholar 

  132. Ren J, Yang Y, Xue J, Xi Z, Hu L, Pan S-J et al (2018) Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via inhibition of miR-5095. Biochem Biophys Res Commun 496(2):712–718

    Article  CAS  PubMed  Google Scholar 

  133. Wu Y, Qian Z (2019) Long non-coding RNAs (lncRNAs) and microRNAs regulatory pathways in the tumorigenesis and pathogenesis of glioma. Discov Med 28(153):129–138

    CAS  PubMed  Google Scholar 

  134. Lan X, Liu X, Sun J, Yuan Q, Li J (2019) CircRAD23B facilitates proliferation and invasion of esophageal cancer cells by sponging miR-5095. Biochem Biophys Res Commun 516(2):357–364

    Article  CAS  PubMed  Google Scholar 

  135. Funikov SY, Zatcepina O (2017) Regulation of microRNA activity in stress. Mol Biol 51(4):496–505

    Article  CAS  Google Scholar 

  136. Kültz D (2005) Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol 67:225–257

    Article  PubMed  Google Scholar 

  137. Buchberger A, Bukau B, Sommer T (2010) Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol Cell 40(2):238–252

    Article  CAS  PubMed  Google Scholar 

  138. Richter K, Haslbeck M, Buchner J (2010) Life on the verge of death: the heat shock response revisited. Mol Cell 40:253–266

    Article  CAS  PubMed  Google Scholar 

  139. Kroemer G, Pouyssegur J (2008) Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell 13(6):472–482

    Article  CAS  PubMed  Google Scholar 

  140. Spriggs KA, Bushell M, Willis AE (2010) Translational regulation of gene expression during conditions of cell stress. Mol Cell 40(2):228–237

    Article  CAS  PubMed  Google Scholar 

  141. Eshkoor S, Ismail P, Rahman S, Moin S (2011) Does GSTP1 polymorphism contribute to genetic damage caused by ageing and occupational exposure? Arch Ind Hyg Toxicol 62(4):291–298

    CAS  Google Scholar 

  142. Eshkoor SA, Ismail P, Rahman SA, Moin S, Adon MY (2012) The Association of DNA damage level with early age at the occupational exposure in the mechanical workshops workers. Asian J Biotechnol 4(2):83–91

    Article  CAS  Google Scholar 

  143. Eshkoor S, Jahanshiri F, Ismail P, Rahman S, Moin S, Adon M (2012) Association between telomere shortening and ageing during occupational exposure. J Med Biochem 31(3):211–216

    Article  CAS  Google Scholar 

  144. Ong J, Woldhuis RR, Boudewijn IM, van den Berg A, Kluiver J, Kok K et al (2019) Age-related gene and miRNA expression changes in airways of healthy individuals. Sci Rep 9(1):1–8

    Article  Google Scholar 

  145. Campisi J, di Fagagna FA (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8(9):729–740

    Article  CAS  PubMed  Google Scholar 

  146. Kuilman T, Peeper DS (2009) Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 9(2):81–94

    Article  CAS  PubMed  Google Scholar 

  147. Wang E (1997) Regulation of apoptosis resistance and ontogeny of age-dependent diseases. Exp Gerontol 32(4):471–484

    Article  CAS  PubMed  Google Scholar 

  148. Hampel B, Malisan F, Niederegger H, Testi R, Jansen-Dürr P (2004) Differential regulation of apoptotic cell death in senescent human cells. Exp Gerontol 39(11):1713–1721

    Article  CAS  PubMed  Google Scholar 

  149. Krtolica A, Campisi J (2002) Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol 34(11):1401–1414

    Article  CAS  PubMed  Google Scholar 

  150. Rodier F, Campisi J, Bhaumik D (2007) Two faces of p53: aging and tumor suppression. Nucleic Acids Res 35(22):7475–7484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192(4):547–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310(5756):1954–1957

    Article  CAS  PubMed  Google Scholar 

  153. Smith-Vikos T, Slack FJ (2012) MicroRNAs and their roles in aging. J Cell Sci 125(1):7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Huan T, Chen G, Liu C, Bhattacharya A, Rong J, Chen BH et al (2018) Age-associated micro RNA expression in human peripheral blood is associated with all-cause mortality and age-related traits. Aging Cell 17(1):e12687

    Article  Google Scholar 

  155. Brooks-Wilson AR (2013) Genetics of healthy aging and longevity. Hum Genet 132(12):1323–1338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Zovoilis A, Agbemenyah HY, Agis-Balboa RC, Stilling RM, Edbauer D, Rao P et al (2011) microRNA-34c is a novel target to treat dementias. EMBO J 30(20):4299–4308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Deraredj Nadim W, Simion V, Bénédetti H, Pichon C, Baril P, Morisset-Lopez S (2017) MicroRNAs in neurocognitive dysfunctions: new molecular targets for pharmacological treatments? Curr Neuropharmacol 15(2):260–275

    Article  Google Scholar 

  158. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S et al (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308(5723):833–838

    Article  CAS  PubMed  Google Scholar 

  159. Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E et al (2008) Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci 105(14):5614–5619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Im H-I, Hollander JA, Bali P, Kenny PJ (2010) MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci 13(9):1120–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Konopka W, Schütz G, Kaczmarek L (2011) The microRNA contribution to learning and memory. Neuroscientist 1073858411411721

  162. Qiu C, Kivipelto M, von Strauss E (2009) Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci 11(2):111

    Article  PubMed  PubMed Central  Google Scholar 

  163. Shi D, Han M, Liu W, Tao J, Chen L (2020) Circulating MicroRNAs as diagnostic biomarkers of clinical cognitive impairment: a meta-analysis. Am J Alzheimer’s Dis Other Dement 35:1533317520951686

    Article  Google Scholar 

  164. Eshkoor SA, Hamid TA, Mun CY, Ng CK (2015) Mild cognitive impairment and its management in older people. Clin Interv Aging 10:687

    Article  PubMed  PubMed Central  Google Scholar 

  165. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9):735–739

    Article  CAS  PubMed  Google Scholar 

  166. Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM et al (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci 101(1):360–365

    Article  CAS  PubMed  Google Scholar 

  167. Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77–103

    Article  CAS  PubMed  Google Scholar 

  168. Kosik KS (2006) The neuronal microRNA system. Nat Rev Neurosci 7(12):911–920

    Article  CAS  PubMed  Google Scholar 

  169. Hansen K (2012) miRNA-132’s role as a dynamic regulator of memory

  170. Schonrock N, Humphreys DT, Preiss T, Götz J (2012) Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-β. J Mol Neurosci 46(2):324–335

    Article  CAS  PubMed  Google Scholar 

  171. Malmevik J, Petri R, Knauff P, Brattås PL, Åkerblom M, Jakobsson J (2016) Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons. Sci Rep 6(1):1–14

    Article  Google Scholar 

  172. Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D et al (2020) miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells 9(2):276

    Article  CAS  PubMed Central  Google Scholar 

  173. Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med 20(8):460–469

    Article  CAS  PubMed  Google Scholar 

  174. McManus MT (2003) MicroRNAs and cancer. Semin Cancer Biol 13(4):253–258

    Article  CAS  PubMed  Google Scholar 

  175. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269

    Article  CAS  PubMed  Google Scholar 

  176. Rothschild SI (2014) microRNA therapies in cancer. Mol Cell Ther 2(1):7

    Article  PubMed  PubMed Central  Google Scholar 

  177. Balacescu O, Visan S, Baldasici O, Balacescu L, Vlad C, Achimas-Cadariu P (2018) MiRNA-based therapeutics in oncology, realities, and challenges. Antisense Therapy

  178. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9):2999–3004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Tili E, Michaille J-J, Cimino A, Costinean S, Dumitru CD, Adair B et al (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179(8):5082–5089

    Article  CAS  PubMed  Google Scholar 

  180. Jiang S, Zhang H-W, Lu M-H, He X-H, Li Y, Gu H et al (2010) MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Can Res 70(8):3119–3127

    Article  CAS  Google Scholar 

  181. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102(39):13944–13949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Iorio MV, Piovan C, Croce CM (2010) Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta BBA Gene Regul Mech 1799(10):694–701

    Article  CAS  Google Scholar 

  183. Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM (2006) Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev 20(16):2202–2207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Chang T-C, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26(5):745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Han C, Yu Z, Duan Z, Kan Q (2014) Role of microRNA-1 in human cancer and its therapeutic potentials. BioMed Res Int 2014:875

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Regionshospitalet Randers, Randers, Denmark, 8930

    Sima Ataollahi Eshkoor

  2. Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada

    Nooshin Ghodsian

  3. Department of Public Health, Faculty of Health, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mehrnoosh Akhtari-Zavare

  4. Department of Akutafdeling, Nykøbing F. Sygehus, 4800, Nykøbing F., Denmark

    Sima Ataollahi Eshkoor

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SAE involved in contributions to the conception, design of the work, and drafted the work or substantively revising. NG involved in contributions to drafting the article and revising. MA-Z involved in contributions to drafting the article and revising. All authors read and approved the final manuscript.

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Eshkoor, S.A., Ghodsian, N. & Akhtari-Zavare, M. MicroRNAs influence and longevity. Egypt J Med Hum Genet 23, 105 (2022). https://doi.org/10.1186/s43042-022-00316-7

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