TABLE 1.
Up-regulated miRNAs in cerebral I/R injuries.
| miRNA | miRNA or agmonir effect | Study type | References |
| miR-106b-5p | ↑ ROS production, ↓antioxidant ability (SOD) and ↑ apoptosis activation |
Experimental (Rat model and PC12 cell line) | Li et al., 2017a |
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| miR-124 | Biomarker of AIS | Clinical | Weng et al., 2011; Rainer et al., 2016 |
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| miR-124 | ↓ p-STAT3, ↓ pyroptosis |
Experimental (Rat model) | Sun et al., 2020a |
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| miR-125b | ↓ CK2α; ↑ NOX2 and NOX4 activation, ↑ ROS |
Experimental (Rat model and PC12 cell line) | Liang et al., 2018 |
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| miR-125b | ↓ Protein kinase CK2 | Experimental (PC-12 cell line) | Liang et al., 2018 |
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| miR-128 | ↓ proliferation ability ↓ GFAP and MAP2 ↑ TNF-α, IL-6, and IL-1β↓ GSH and SOD ↑ MDA ↓ ARPP21 and CREB1 ↓ BDNF |
Clinical and Experimental (Mouse model and hippocampal neurons and astrocytes) | Chai et al., 2021 |
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| miR-128-3p | ↓ Nrf2, ↓ antioxidant ability |
Experimental (Rat model and neural stem cells line) | Li et al., 2019a |
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| miR-142-5p | ↓ Nrf2/ARE, ↑ ROS |
Experimental (Rat model and primary hippocampal neurons) | Wang et al., 2017 |
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| miR-143-3p | ↓ FSTL1, Bcl-2, ↑ Bax, caspase 3 and cleaved caspase 3, ↑ apoptosis |
Experimental (Mice model and human neuroblastoma cell line SH-SY5Y) | Wang and Liu, 2021 |
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| miR-145 | ↑ ERK, p38 and MAPK ↑ Cyclin D1, Nestin, NSE, and GFAP ↓ Cleaved-caspase 3 ↑ NSCs proliferation ↑differentiation of NSCs ↓ apoptosis |
Experimental (Rat model and Rat neural stem cells) | Xue et al., 2019 |
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| miR-150 | ↓ BBB permeability ↑ Tie-2 ↓ claudin-5 |
Experimental (Rat model and BMECs cell line) | Fang et al., 2016, 2 |
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| miR-153 | ↓ Nrf2 and HO-1, ↓ antioxidant levels, ↑ ROS |
Experimental (Primary hippocampal neurons) | Ji et al., 2017 |
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| miR-16 | Biomarker of AIS | Clinical | Rainer et al., 2016 |
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| miR-181a | ↓ XIAP, Bcl-2, ↑ Bax, cleaved caspase 3, ↑ apoptosis |
Experimental (Rat model and primary cortical neurons) | Zhang et al., 2019a |
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| miR-182 | ↓ mTOR/ ↓ FOXO1 ↓ ZO-1, Occludin, and Claudin-5 ↓ Bcl-2/Bax |
Experimental (Mouse model and primary cultures of astrocytes, mouse brain vascular pericytes, N2a mouse neuroblastoma cell line and BV2 microglial cells) | Zhang et al., 2020b |
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| miR-187-3p | ↓ Seipin, ↑ apoptosis, ↓ autophagy |
Experimental (PC12 cells) | Ren et al., 2020 |
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| miR-191-5p | ↓ BDNF | Experimental (Mouse model) | Wu et al., 2021 |
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| miR-195-5p and miR-451a | ↓ BDNF ↓ VEGF-A |
Clinical | Giordano et al., 2020 |
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| miR-19a-3p | ↑ TNF-α, IL-1β, IL-6 ↓ Bcl-2, ↑ Bax ↓ IGFBP3 ↓ cell viability |
Experimental (rat model and SH-SY5Y cell line) | Chai et al., 2020 |
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| miR-200a | ↑ STAT and MAPK, ↑Bax/Bcl-2, p53, cytochrome c, ↑ apoptosis |
Experimental (Neural stem cells) | Ma et al., 2017a |
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| miR-200a-3p | ↑ neuronal cell death, ↑ ROS levels |
Experimental (HT-22 cells) | Wei et al., 2015 |
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| miR-200b-3p | ↑ neuronal cell death, ↑ ROS levels |
Experimental (HT-22 cells) | Wei et al., 2015 |
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| miR-20a | ↑ Cadherin 1 | Experimental (Rat model) | Yang et al., 2021 |
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| miR-210 | ↑HIF-1α, VEGF, caspase-3, ↑ apoptosis |
Experimental (Rat model and rat neuronal cells) | Sun et al., 2019 |
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| miR-23a-3p | ↓ NO, 3-NT ↑ MnSOD, ↑ antioxidant ability, ↓ caspase 3, ↓ ROS, ↓ apoptosis |
In vivo and in vitro (Mice model and neuro-2a cells) | Zhao et al., 2014 |
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| miR-29b | ↑ caspase 3, ↓ Bcl-2, MCL-1, ↑ apoptosis |
Experimental (neuro-2a cells) | Huang et al., 2018 |
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| miR-302b-3p | ↓ Nrf2/ARE, FGF15, ↑ caspase 3, ↑ ROS, ↑ apoptosis |
Experimental (Murine HT22 cell line) | Zhang et al., 2019b |
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| miR-30a | ↑ BBB permeability ↑ zinc accumulation ↓ ZnT4 ↓ occludin and claudin-5 |
Experimental (Rat model and Brain microvascular EC bEnd3 cell line, pericyte cell line MBVP, astrocytic cell C8-D1A) | Wang et al., 2021c |
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| miR-339 | ↓ FGF9 and CACNG2 ↓ Cell Proliferation ↑ Induces Apoptosis ↑ p-P38 and p-JNK |
Experimental (PC12 cells) | Gao et al., 2020, 2 |
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| miR-421 | ↓ SOD, ↑ ROS, ↑ apoptosis |
Experimental (Rat model and PC12 rat pheochromocytoma cell line) | Yue et al., 2020 |
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| miR-424 | ↑ Nrf2, ↑ antioxidant responses, ↓ROS |
Experimental (Mouse model) | Liu et al., 2015 |
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| miR-429 | ↑ neuronal cell death, ↑ ROS levels |
Experimental (HT-22 cells) | Wei et al., 2015 |
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| miR-670 | ↓ Hippo-Yap, ↑ apoptosis |
Experimental (Mouse model and neuro-2a cells) | Yu et al., 2021c |
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| miR-670 | ↓ phosphorylation of downstream Yap ↓ Yap degradation. |
Experimental (Mouse model and neuro-2a cells) | Yu et al., 2020 |
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| miR-7-5p | ↓ Sirtuin 1, ↑ apoptosis |
Experimental (Rat model and SH-SY5Y cells) | Zhao and Wang, 2020 |
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| miR-9 | Biomarker of AIS | Clinical | Ji et al., 2016 |
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| miR-93 | ↓ Nrf2 and HO-1, ↓ antioxidant levels, ↑ ROS |
Experimental (mice model and primary cortical neurons) | Wang et al., 2016 |
ACSL4, acyl-CoA synthetase long chain family member 4; AIM, absent in melanoma; AIS, acute ischemic stroke; Akt, Protein kinase B; ARE, antioxidant response element; AQP, Aquaporin; BBB, blood-brain barrier; BBC3, Bcl-2-binding component 3; BDNF, Brain-derived neurotrophic factor; CCL, C-C Motif Chemokine Ligand; CXCL, C-X-C motif ligand; CXCR, C-X-C motif chemokine receptor; FIP, FAK family-interacting protein; FOXO1, Forkhead box class O1; FSTL1, follistatin-like protein 1; GPX4, glutathione peroxidase 4; GSK, glycogen synthase kinase; HDAC, histone deacetylase; HIF, hypoxia inducible factor; HO-1, heme oxygenase 1; IGFBP3, Insulin Like Growth Factor Binding Protein 3; IL, interleukin; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; MCL, myeloid leukemia sequence; MDA, malondialdehyde; miR, microRNA; MnSOD, manganese superoxide dismutase; mTOR, mammalian target of rapamycin; NEAT, nuclear paraspeckle assembly transcript; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; 3-NT, 3-nitrotyrosine; NOX, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; Nrf2, nuclear factor-erythroid factor 2-related factor 2; PI3K, Phosphoinositide 3-kinase; PUMA, p53-up-regulated modulator of apoptosis; SOD, super oxide dismutase; p-STAT, phosphorylated (activated) signal transducer and activator of transcription; RBFox-1, RNA-binding protein fox-1 homolog 1; SNAI2, Snail Family Transcriptional Repressor 2; SOX7, SRY-Box Transcription Factor 7; TFR1, transferrin receptor 1; TLR4, Toll-like receptor 4; TNF, tumoral necrosis factor; TP53INP1, Tumor Protein P53 Inducible Nuclear Protein 1; VEGF, vascular-epithelial growth factor; XIAP, X chromosome-linked inhibitor of apoptosis protein; ZO, zonula occludens.