Table 3.
The lncRNA-miRNA-mRNA axis in cerebral I/R.
| Models | Species | Cell dysfunction | Expression | lncRNA | miRNA | mRNA | Function | Mechanism | Relationship | Prediction tool | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|
| MCAO/R in mice and mice primary astrocytes under OGD/R condition | Mouse | Apoptosis | ↑ | MALAT1 | miR-145 | AQP4 | Knockdown of MALAT1 increased cell viability and reduced cell apoptosis in MA-C cells | miR-145 was identified as a potential target of MALAT1 | NR | starBase; TargetScan | [95] |
| Mouse primary BMECs under OGD/R condition | Mouse | Autophagy | ↑ | MALAT1 | miR-26b | ULK2 | MALAT1 promoted BMEC autophagy and survival under OGD/R condition | MALAT1 served as a ceRNA by sponging miR-26b | NR | lncRNA database v2.0; miRDB | [107] |
| MCAO/R in mice and mice primary cortical neurons under OGD/R condition | Mouse | Autophagy | ↑ | MALAT1 | miR-30a | Beclin1 | Downregulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo | May serve as a molecular sponge for miR-30a | NR | RNA hybird; starBase v.2.0 | [108] |
| MCAO/R in mice and primary mouse astrocytes under OGD/R condition | Mouse | Apoptosis | ↑ | TUG1 | miR-145 | AQP4 | Knockdown of TUG1 decreased lactate dehydrogenase levels and the ratio of apoptotic cells and promoted cell survival in vitro and reduced the infarction area and cell apoptosis in I/R mouse brains in vivo | May function as a ceRNA for miR-145 | NR | Bioinformatic analysis | [96] |
| tMCAO/R in rats and PC-12 cells under OGD/R condition | Rat | Proliferation; apoptosis; inflammation | ↑ | H19 | miR-138-5p | p65 | H19 promotes inflammatory response and improved neurological function in tMCAO rat model | Negatively regulated miR-138-5p expression | NR | n/a | [97] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | H19 | miR-148a-3p | Rock2 | lncRNA-H19 altered OGD/R-induced oxidative stress | May act as a molecular sponge of miR-148a-3p | NR | starBase | [99] |
| MCAO/R in rats and neuronal cells under OGD/R condition | Human; rats | Apoptosis | ↑ | H19 | miR-19a | Id2 | Knockdown of H19 alleviated cell apoptosis, significantly decreased neurological deficit, brain infarct volume, and neuronal apoptosis | miR-19a directly binds to H19 | NR | starBase 2.0 | [98] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↓ | Rian | miR-144-3p | GATA3 | Overexpression of Rian could inhibit the cell apoptosis induced by OGD and distinctly reduce the infarct size | miR-144-3p directly interacts with Rian | NR | DIANA online tools | [100] |
| MCAO/R in rats and SK-N-SH and SH-SY5Y cells under OGD/R condition | Rat | Pyroptosis | ↑ | MEG3 | miR-485 | AIM2 | Knockdown of MEG3 inhibited OGD/R-induced pyroptosis and inflammation, and inhibited Caspase-1 signaling and decreased the expression of AIM2, ASC, cleaved-Caspase-1 and GSDMD-N | Acted as a molecular sponge to suppress miR-485 | NR | n/a | [114] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | MEG3 | miR-21 | PDCD4 | Knockdown of MEG3 protects against ischemic damage and improves overall neurological functions in vivo | Functions as a ceRNA for directly binding to miR-21 | NR | lnCeDB | [144] |
| N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | Gm11974 | miR-766-3p | NR3C2 | Knockdown of lncRNA Gm11974 alleviated the apoptosis induced by OGD and cell death rates were significantly reduced | Could negatively regulate the expression of miR-766-3p | NR | Bioinformatics software | [101] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | Oprm1 | miR-155 | GATA3 | Overexpression of lncRNA Oprm1 alleviated the apoptosis induced by OGD and distinctly decreased infarct size | miR-155 is a direct target of lncRNA Oprm1 | NR | TargetScan | [102] |
| tMCAO/R in mice and N2a cells under OGD/R condition | Human; mouse | Autophagy | ↑ | KCNQ1OT1 | miR-200a | FOXO3/ATG7 | Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in tMCAO mice and might inhibit I/R-induced autophagy and increase cell viability | Acted as a ceRNA of miR-200a | NR | Lncbase | [109] |
| Mice primary cortical neurons under OGD/R condition | Mouse | Apoptosis | ↑ | KCNQ1OT1 | miR-9 | MMP8 | KCNQ1OT1 regulates OGD/R-induced injury in cultured primary cortical neurons via modulating miR-9/MMP8 axis as a ceRNA | Directly binds to miR-9 | NR | Bioinformatic analysis | [106] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | AK038897 | miR-26a-5p | DAPK1 | AK038897 knockdown protected against MCAO/R-induced brain injury and neurological deficits in vivo | Functions as a ceRNA for miR-26a-5p | NR | starBase; TargetScan | [103] |
| MCAO/R in mice and N2a cells under OGD/R condition | Mouse | Apoptosis | ↑ | CHRF | miR-126 | SOX6 | CHRF knockdown in vivo markedly prevented ischemic damage and alleviated neurological dysfunctions | Played as a ceRNA to direct binding with miR-126 | NR | TargetScan | [104] |
| SH-SY5Y cells under OGD/R condition | Human | Apoptosis | ↓ | SNHG16 | miR-106b-5p | LIMK1 | lncRNA SNHG16 promoted OGD/R-induced SH-SY5Y cell survival and suppressed its apoptosis and Caspase-3 activity | Directly targeted miR-106b-5p | NR | starBase; MiRTarBase | [105] |
| MCAO/R in rats and PC-12 cells under OGD/R condition | Rat | Inflammation | ↑ | SNHG14 | miR-136-5p | ROCK1 | Interference of SNHG14 by shRNA vector enhanced neuron survival and suppressed inflammation in response to OGD/R insult. SNHG14 promoted neurological impairment and inflammatory response | Acting as a sponge of miR-136–5p | NR | starBase | [113] |
| N2a cells under OGD/R condition | Mouse | Proliferation; apoptosis | ↑ | SNHG12 | miR-199a | SIRT1 | Knockdown SNHG12 inhibited cell proliferation under OGD/R condition | SNHG12 blocks the expression of miR-199a | NR | http://microRNA.org | [110] |
| Mouse primary BMECs under OGD/R condition | Mouse | Cell death; inflammation | ↑ | SNHG12 | miR-199a | n/a | Overexpression of SNHG12 inhibited BMEC death and the inflammatory response but promoted angiogenesis after OGD/R | Directly targets miR-199a | NR | miRcode | [111] |
| Mouse primary BMECs under OGD/R condition | Mouse | Cell death; migration | ↑ | SNHG1 | miR-199a | HIF-1α; VEGF | Promoted BMEC survival under OGD/R condition, and angiogenesis after OGD/R treatment | Snhg1 targets miR-199a by binding to complementary miR-199a seed regions | NR | miRDB | [112] |
↑: the upward arrow indicates increased expression of lncRNAs; ↓: the downward arrow indicates decreased expression of lncRNAs; n/a: not applicable; NR: lncRNAs negatively regulate miRNAs; PR: lncRNAs positively regulate miRNAs; RC: reciprocal correlations between lncRNAs and miRNAs; tMCAO/R: transient middle cerebral artery occlusion/reperfusion; OGD/R: oxygen-glucose deprivation and reperfusion; BMECs: brain microvascular endothelial cells; ceRNA: competing endogenous RNA; Rian: RNA imprinted and accumulated in nucleus; MALAT1: metastasis-associated lung adenocarcinoma transcript 1; TUG1: taurine-upregulated gene 1; MEG3: maternally expressed gene 3; CHRF: cardiac hypertrophy-related factor; HOTAIR: HOX transcript antisense RNA; SNHG1/12/14/16: small nucleolar RNA host gene 1/12/14/16; LIMK1: the LIM motif-containing protein kinase family-contained LIM kinase 1; KCNQ1 opposite strand/antisense transcript 1; MMP-8: matrix metalloproteinase-8; Id2: inhibitor of DNA binding/differentiation 2; GATA3: GATA-binding protein 3; ULK2: Unc-51-like kinase 2; AQP4: aquaporin 4; Rock2: Rho-associated protein kinase 2; AIM2: absent in melanoma 2; SOX6: sex-determining region Y box 6; HIF-1α: hypoxia inducible factor-1α; VEGF: vascular endothelial growth factor; SIRT1: sirtuin 1; GATA3: GATA-binding protein 3; ROCK1: Rho-associated coiled-coil-containing protein kinase 1; FOXO3: forkhead box O3; ATG7: autophagy-related gene 7; DAPK1: death-associated protein kinase 1; NR3C2: nuclear receptor subfamily 3 group C member 2.