Table 2 Examples of miRNAs, targets and functions involved

1

miR-1

IGF1 and HDAC4, mTORmiR1HDAC4follistatin pathway, Notch signaling pathway

Differentiation of cardiac muscle, skeletal muscle differentiation following aging, inhibit tumor growth and metastasis, cognition

[37,38,39]

2

Let-7

DAF-12 signaling pathway, insulin/IGF signaling (IIS) pathway, LOX-1-ROS-p38MAPK-NF-κB signaling pathway, LOX-1-ROS-PKB-eNOS pathway, TGF‐β pathway, RAS and KIT signaling pathways

Senescence, age-dependent changes in the vasculature and vascular aging, tumor suppressor and oncogene, apoptosis, migration, and invasion, potential diagnostic and prognostic marker, neurodegeneration

[2, 40,41,42,43,44]

4

MiR-9

HIF-1α-VEGF signaling pathway, p16-Prb pathway

Neurogenesis, angiogenesis, regulation of lymphatic inflammatory and lymphangiogenic pathways, cognition, cell proliferation, migration, invasion and angiogenesis

[45, 46]

5

miR-17

the P53, ERB, and MAPK signaling pathways

Autophagy, apoptosis, growth, chemoresistance, regulated genes involved in cell cycle control and tumor development, aging, cognition

[47,48,49]

6

MiR-21

RasA1 signaling pathway KRAS, RAS/MEK/extracellular signal-regulated kinase (ERK) signaling pathway, PI3K/AKT pathway

Promotes cell proliferation, anti-apoptosis signaling and malignant transformation, inflammation-related miRNAs, advanced oxidation protein products (AOPP), with the presence of frailty, age-related frailty

[50,51,52]

7

MiR-26b

Rb1-E2F and p27(kip1) pathways, Wnt-β-catenin signaling pathway,

Cell cycle influence

[53]

8

MiR-29a

MMP2 signaling pathway, Smad4-dependent way, TGF-β signaling pathway, Wnt-β-catenin signaling pathway, PTEN/AKT/GSK3β signaling pathway, TGF-beta1/miR-29a/HDAC4 pathway, Hedgehog signaling pathway, NF-κB pathway, p42-44 MAPK pathway and Wnt-β-catenin pathway

Cell proliferation, apoptosis, angiogenesis, invasion, metastasis, drug resistance and chemotherapy resistance

[54, 55]

9

MiR-29b

PI3K-Akt signaling pathways, PTEN/AKT/β-catenin signaling pathway, AKT/GSK-3β/β-catenin signaling pathway, AKT/mTOR pathway, PTEN/AKT/GSK-3β/β-catenin signaling pathway. Wnt-β-catenin pathway

Effect on tumor suppressive genes, aggressiveness and prognosis of malignant neoplasms, cell cycle regulation, fibrosis and neuronal regulations, tumorigenesis and cellular senescence, osteogenic differentiation

[54,55,56,57,58]

10

miR-30a

TOR pathway, Wnt pathway, Fgf signaling pathway, Wnt/β-catenin pathway, MTDH/PTEN/Akt pathway, PI3K signaling pathway, PI3K/Akt/mTOR signaling pathway, EZH2/miR-30a/KPNB1 signaling pathway

Inhibiting proliferation, invasion, and migration, inducing apoptosis. synaptic plasticity and cognition

[2, 59, 60]

11

MiR-31

RAS/MAPK pathway, RAS/MARK pathway PI3K/AKT pathway, RB/E2F pathway, P53 pathway, Rho/ROCK pathway, NF-κB pathway, E2F pathway, WNT pathway,

Proliferation, Tumorigenesis, migration, anti-apoptosis, improving cognition

[61,62,63,64]

12

MiR-34

MEK/ERK signaling pathway, E2F pathway

Inhibits the cell cycle and cell proliferation

[65]

13

miR-34a

FoxM1/c-Myc pathway, p53 pathway, HIF-1a pathway

Cell cycle influence, response to hypoxia stress

[2, 53, 66]

14

miR-71

p38 pathway, KGB-1 on DAF-16 involved pathways, PI3K pathway, UNC-31–mediated InsR/PI3K signaling

Long-term survival

[67,68,69]

15

miR-100

FGFR3 pathway, HIF-1α and HIF-2α dependent pathway, mTOR pathway, MAPK pathway, PI3K pathway, PKB pathway

Subtle, maintaining cell viability, cognition

[2, 70, 71]

16

MiR-107

Wnt/β-catenin signaling pathway,

Cell cycle influence, the progression of cell growth, migration, and invasion in various cancers,

[72]

17

MiR-124

Notch signaling pathway, miR124/AMPK/mTOR pathway, miR-124-STAT3 pathway, TLR signaling pathway, JNK and p38 pathways, MiR-124-PTPN1 signaling pathway

Proliferation, differentiation, proliferation, apoptosis, and growth of cells as well as immunity

[73, 74]

18

MiR-125b

NF-kB pathway, CDKN2A pathway, p53 pathway, PI3K/Akt/mTOR pathway, ErbB2 pathway, Wnt pathway,

Proliferation, differentiation, metabolism, apoptosis, drug resistance, tumor immunity, diagnosis, prognosis and clinical treatment of tumors, neuron inflammation

[53, 75]

19

MiR-132

HIF-1α pathway, PTEN/AKT/FOXO3 signaling pathway, AKT signaling pathway,

Neuronal health, neuron morphogenesis and plasticity, suppresses the migration and invasion of cancer

[2, 76,77,78,79]

20

MiR-137

miR-137/Src/MAPK signaling pathway, ERK1/2 pathway

Neuroprotective effects, neural development, neoplastic transformation, act as a tumor suppressor, cell proliferation, differentiation, migration and metastasis, and induce cell cycle arrest, differentiation and apoptosis

[80, 81]

21

MiR-146

RAS pathway, NOTCH pathway, NF-κB pathway;

Cell proliferation, invasion, and metastasis, act as a tumor suppressor, inflammation

[82,83,84]

22

MiR-146a

NF-kB pathway, TLR4/NF-κB pathway, TNFα inflammatory pathway, IL-1α signaling pathway

Neuroinflammation, Amyloid-beta deposition, inflammation, innate immunity, and cancer, as well as to regulate mitochondrial functions, inflammation-aging, inhibition of proinflammatory pathways

[51, 53, 85, 86]

23

MiR-155

BCR pathway, Toll-like receptor (TLR) pathway, ERK pathway, c-Jun N-terminal kinase pathway (JNK), SOCS1 pathway, JAK2/STAT3 pathway, RhoA pathway, PI3K/AKT pathway

Tumor inflammation and growth, chemotherapy resistance, regulates immune system including B cells and T cells. cognition

[87,88,89,90]

24

miR-199a

HIF-1α pathway, Toll-like receptor signaling pathway, insulin signaling pathway, adipocytokine signaling pathway (KEGG), PI3K/AKT/mTOR signaling pathway, Wnt/β-catenin signaling pathway

Master regulators for cellular processes, function in immune system, potent tumor suppressor, cognition, proliferation, migration, invasion, apoptosis, autophagy and glycometabolism

[2, 91,92,93,94]

25

Mir-206

IGF1 pathway, MRFs pathway, BDNF pathway, Fstl1 pathway, MEF2 pathway, IL-17 pathway, HIF-1α pathway; WNT signaling pathway; mitochondrial apoptosis pathway;

Neuronal differentiation, brain development, functions in neuromuscular synapse development and maintenance, muscle cell proliferation; inhibits tumor cell proliferation, migration, and invasion, and induces apoptosis

[37, 95, 96]

26

MiR-210

Increased ROS pathway, protein kinase B (Akt) pathway and p53-dependent pathway, mTOR pathway, HIF-1α pathway, PI3K pathway, Akt pathway, ERK pathway, NFκB pathway, p53 pathway

Amyloid-beta deposition, mitochondrial metabolism, angiogenesis, the DNA damage response, cell proliferation, apoptosis

[53, 85, 97]

27

miR-211‐5p

Ezrin/Fak/Src signaling pathway, JAK/STAT3 pathway, PERK pathway, MiR-211-5p-NUAK1 Pathway

Aging, proliferation, prognosis in various cancers, apoptosis, cell proliferation, invasion, apoptosis and immunity, cognition

[41, 98, 99]

28

MiR-212

Sirtuin signaling pathway, Hedgehog signaling pathway, Wnt/βcatenin pathway, AKT signaling pathway,

Serve as an oncogene or tumor suppressor, oncogenesis, development and metastasis of cancer, proliferation, invasion, Metastasis, cognition, life span

[76, 79, 100, 101]

29

MiR-217

Sirtuin signaling pathway, HIF-1α pathway, MAPK signaling pathway,

Hemostasis, normal growth, and maintenance of cells, proliferation, apoptosis, transcription regulation and development, invasion, drug resistance

[2, 102]

30

MiR-221

PTEN pathway, AKT pathway, JAK/STAT3 signaling pathway, PTEN-mediated PI3K/Akt pathway

Tumorigenesis and progression, chemotherapy resistance, cancer cell proliferation, invasion and metastasis, stemness promotion, cell survival, the relapse of cancer cells, cognition, life span?

[2, 49, 103,104,105]

31

MiR-222

PTEN pathway, p27kip1 and c-kit pathway, PTEN-mediated PI3K/Akt pathway; p53 pathway

Tumor initiation and progressions, cancer cell proliferation, invasion and metastasis, stemness promotion, cell survival, chemoresistance, the relapse of cancer cells, cognition,

[2, 48, 103, 104, 106]

32

miR-320

insulin/IGF signaling (IIS) signaling pathway, AQP1-mediated proliferative signaling pathway,

Neurodegenerative disease, tumor suppressor, to promote tumorigenesis, life span

[2, 107,108,109]

33

MiR-340‐3p

mTOR pathway

Affecting life span, Tumoral survival, Human longevity

[48, 110, 111]

34

MiR-371–3

PLA2/PKCα signaling pathway

tumor growth and metastasis, drug resistance, overall survival

[61, 112]

35

MiR-374a‐5p

mTOR signaling pathway

Proliferation, migration, invasion, chemoresistance, prognosis, life span, cognition

[113,114,115]

36

MiR-376c‐3p

Wnt/β-catenin pathway

Life span, cell cycle progression, proliferation, migration, invasion, survival and poorly response to chemotherapy, inhibits apoptosis, cognition

[55, 116,117,118]

37

miR-483

Wnt/β-catenin signaling pathway, glucose/OGT/miR-483-3p signaling pathway, MAPK/ERK pathway, TGF-β pathway,

Antiaging properties, inflammation, proliferation, apoptosis, promote tumor development

[51, 119]

38

MiR-484

mTOR signaling pathway, Hippo signaling pathway, estrogen signaling pathway, interferon pathway

Mitochondrial fission, synaptic transmission and regulation of synaptic plasticity, synaptic function, ATP generation, presynaptic calcium level, oncogene, tumor suppressor, negative prognostic biomarker

[120,121,122]

39

MiR-567

PI3K/AKT/c-Myc pathway, cMras/miR-567/PTPRG regulatory pathway;

Biological processes in the neuronal cells, neuronal differentiation and brain development, tumorigenesis and development, cell proliferation, migration and invasion, induced G1/S transition, chemoresistance, tumor suppressor;

[123,124,125,126,127,128]

40

MiR-1225‐3p

mTOR/p70S6K pathway, Melatonin pathway, MMEJ pathway,

Life span, role in repairing single-strand breaks during DNA replication, uncontrolled proliferation and progression of cancer,

[129,130,131]

41

MiR-5095

Wnt/b-catenin signaling pathway, melatonin pathway

Life span, inhibited cell proliferation, migration and invasion of glioblastoma; esophageal tumor development and progression

[129, 132,133,134]