Table 1.
Summary of the mechanisms of lncRNAs in cerebral ischemia.
| Author | LncRNA | Models/diseases | Species/cell source species | Targets | Pathway | Functions | Reference |
|---|---|---|---|---|---|---|---|
| Yin et al., 2019 | SNHG12/LNC04080 | MCAO, OGD/R | Mus musculus | miR-199a | Up-regulate SIRT1 | SNHG12 targets miR-199a to upregulate SIRT1 expression, thereby attenuating cerebral ischemia/reperfusion injury through AMPK pathway activation. | (21) |
| Long et al., 2018 | SNHG12/LNC04080 | OGD/R | Mus musculus | miR-199a | Inhibit t-he expression of E-selectin, MCP 1, IL 6, and promote the expression of FGFb | SNHG12 inhibits OGD/R-induced endothelial cell injury, inflammatory response and angiogenesis by targeting miR-199a | (22) |
| Zhang et al., 2017b | MALAT1 | MCAO, OGD/R | Rattus norvegicus | Not known | Promotes IL-6, MCP1 and E-selectin expression | Malat1 exerts anti-apoptotic and anti-inflammatory effects in the cerebral microvasculature to reduce ischemic cerebrovascular and parenchymal damage. | (23) |
| Zhang et al., 2018 | MALAT1 | MCAO, OGD/R | Mus musculus | miR-145 | Involve in 15-LOX1/STAT3 signaling pathway | MALAT1 may regulate angiogenesis through the 15-LOX1/STAT3 signaling pathway, which may provide a key target for the treatment of hypoxic injury and a pathway for therapeutic angiogenesis. | (24) |
| Zhang et al., 2017b | MALAT1 | MCAO, OGD/R | Rattus norvegicus | miR-375 | Targeting PDE4D | Inhibition of MALAT1 attenuated CI/RI in rats by modulating the miR-375/PDE4D axis, inhibiting ROS levels, inflammatory factor levels, and apoptosis. | (23) |
| Wang et al., 2020a | MALAT1 | MCAO, OGD/R | Mus musculus | miR-145 | Inhibit AQP4 | MALAT1 affects AQP4 expression by competitively binding to miR-145, thereby promoting cerebral ischemia-reperfusion injury. | (25) |
| Deng 2021 | ANRIL | MCAO, OGD/R | Mus musculus | miR-671 | Inhibit NF-κB signaling | Down-regulation of ANRIL reduces neuroinflammation by negatively regulating miR-671-5p to suppress NF-κB in IS models, providing a rationale for the protective effect of down-regulation of ANRIL in IS patients. | (26) |
| Feng et al., 2019 | ANRIL | Acute ischemic stroke | Homo sapiens | Not known | Decrease CRP, TNF-α, IL-6, and promote IL-10 | Downregulation of the circulating lncRNA ANRIL is associated with increased stroke risk, increased disease severity, and increased inflammation in patients with AIS. | (27) |
| Wang et al., 2017 | H19 | MCAO | Mus musculus | Not known | Reduce TNF-α and CD11b, increase Arg-1, CD206, IL-10 | H19 promotes neuroinflammation by driving HDAC1-dependent M1 microglial polarization. | (28) |
| Wang et al., 2018b | NKILA | OGD/R | Mus musculus | miR-103 and miR-107 | Inhibit NF-κB signaling | OGD/R induces upregulation of NKILA to inactivate NF-κB signaling, which mediates subsequent neuronal cell death. | (29) |
| Sun et al., 2021 | SNHG14 | OGD/R | Mus musculus | miR-30b-5p | Promote the expression of Atg5 and Beclin 1 | SNHG14 promotes the expression of Atg5 and Beclin 1 by sponging miR-30b-5p, thereby activating autophagy and aggravating cerebral ischemia-reperfusion injury. | (30) |
| Qi et al., 2017 | SNHG14 | OGD/R | Mus musculus | miR-145-5p | Promote TNF-α and NO | Long non-coding RNA SNHG14 promotes microglial activation in cerebral infarction by regulating miR-145-5p/PLA2G4A | (31) |
| Zhang et al., 2021b | SNHG14 | OGD/R | Mus musculus | miR-199b | Promote AQP4 | Knockdown of SNHG14 attenuates ischemic brain injury by suppressing inflammation and oxidative stress through the miR-199b/AQP4 axis. | (32) |
| Zhong et al., 2019 | SNHG14 | OGD/R | Mus musculus | miR-136-5p | Promote ROCK1 | SNHG14 promotes neural injury and inflammatory responses by increasing ROCK1 expression while reducing miR-136-5p levels in OGD/R-induced injury. | (33) |
| Sun et al., 2022 | SNHG15 | MCAO | Mus musculus | Not known | Promote the expression of p-STAT6 | SNHG15 is a negative regulator of stroke-induced immunosuppressive inflammation. | (34) |
| Hu et al., 2021 | SNHG15 | OGD/R | Mus musculus | miR-302a-3p | Activiate STAT1/NF-κB pathway | Inhibition of SNHG15 ameliorated ischemia/hypoxia-induced neuronal damage and microglial inflammation by modulating the miR-302a-3p/STAT1/NF-κB pathway. | (35) |
| Zhang et al., 2020a | SNHG4 | MCAO | Rattus norvegicus | miR-449c-5p | Up-regulate p-STAT6 | SNHG4 regulates STAT6 and suppresses inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury. | (36) |
| Deng et al., 2019 | Nespas | MCAO | Mus musculus | Not known | Inhibite NF-κB signaling | Nespas exerts anti-inflammatory and anti-apoptotic effects by inhibiting TRIM8-associated K63-linked polyubiquitination of TAK1. | (37) |
| Zhang and Zhang 2020 | ZFASI | MCAO, OGD/R | Rattus norvegicus | miR-582-3p | Decrease Bax, Caspase-3, TNF-α, IL-1β, MCP-1, and increase Bcl-2 | The lncRNA ZFAS1 protects neurons from injury and modulates inflammation, oxidative stress, apoptosis, cerebral ischemia-reperfusion injury by regulating miR-582-3p and NO levels. | (38) |
| Zhang et al., 2021c | MIAT | MCAO/R | Mus musculus | miR-874-3p | Decrease IL-1β | Lnc RNA MIAT impairs neural function in ischemic stroke by targeting IL1B by upregulating microRNA-874-3p | (39) |
| Wang et al., 2019 | TUG1 | OGD/R | Mus musculus | miR-145a-5p | Decrease TNF-α, IL-6, and increase IL-10; Inhibite NF-κB signaling | Lnc RNA TUG1 sponge Mir-145a-5p regulates microglial polarization | (40) |
| Liang et al., 2020 | MEG3 | MCAO, OGD/R | Rattus norvegicus | miR-485 | Promotes the release of IL-1β and IL-18 | The MEG3/miR-485/AIM2 axis promotes pyroptosis by activating caspase1 signaling during brain I/R. | (41) |
| Li et al., 2020a | MEG3 | OGD/R | Mus musculus | Not known | Decrease CD86, iNOS, TNF-α, IL-1β, and increase CD206, Arg, IL-10, IL-4 | Inhibition of MEG3 can alleviate cerebral ischemia-reperfusion injury by inhibiting M1 polarization and promoting M2 polarization through Krüppel-like factor 4 (KLF4) | (42) |
| Zhang et al., 2019a | 1810034E14Rik | OGD/R | Mus musculus | Not known | Inhibite NF-κB signaling | Overexpression of 1810034E14Rik reduced the expression of inflammatory cytokines, and also inhibited the activation of microglia and inhibited the phosphorylation of p65. | (43) |
| Wang et al., 2020b | Gm15628 | MCAO/R | Mus musculus | Not known | Increase IL-4 | Silencing the LncRNA Maclpil in pro-inflammatory macrophages alleviates stroke via LCP1 | (44) |
| Tian et al., 2021b | SNHG8 | MCAO | Mus musculus | miR-425-5p | Inhibite NF-κB signaling, increase the expression of sirtuin1 | The Snhg8/miR-425-5p/SIRT1/NF-κB axis plays a critical role in regulating cerebral ischemia-induced microglial inflammation and brain-blood barrier damage. | (45) |
| Zhang et al., 2021d | SNHG8 | MCAO, OGD/R | Rattus norvegicus | miR-449c-5p | regulate SIRT1/FoxO1 signaling pathway | SNHG8 inhibits microglial activation and BBB permeability through the miR-449c-5p/SIRT1/FoxO1 pathway, thereby triggering protection against ischemic brain injury. | (46) |
| Jin 2021 | NEAT1 | MCAO | Mus musculus | Not known | Increase IL-1β, IL-6, TNF-α, and decrease IL-4, IL-10; activate JAK-STAT signaling pathway | Knockdown of Neat1 significantly attenuated brain injury by reducing the number of activated microglia and reducing their release of pro-inflammatory cytokines. | (47) |
| Han and Zhou 2019 | NEAT1 | OGD/R | Mus musculus | Not known | Regulate Wnt/β-catenin signaling | YY1-induced upregulation of NEAT1 promotes OGD/R injury and neuroinflammatory injury in microglia via the Wnt/β-catenin signaling pathway. | (48) |
| Zhang et al., 2021 | NEAT1 | OGD/R | Mus musculus | Not known | Activiate caspase-1 | Gastrodin reduces cerebral ischemia/reperfusion injury by inhibiting pyroptosis by regulating the lncRNA NEAT1/miR-22-3p axis | (49) |
| Ni et al., 2020 | NEAT1 | OGD/R | Mus musculus | Not known | Inhibite AKT/STAT3 signaling pathway | The lncRNA NEAT1 may inhibit the polarization of microglia towards the M1 phenotype to reduce OGD/R-induced damage and reduce the activity of the AKT/STAT3 pathway. | (50) |
| Zheng et al., 2021 | OIP5-AS1 | ox-LDL-induced endothelial cell injury | Homo sapiens | miR-98-5p | Regulate TLR4/NF-κB signaling | LncRNA OIP5-AS1 accelerates ox-LDL-induced endothelial cell injury by regulating miR-98-5p-mediated HMGB1 through TLR4/NF-κB signaling pathway. | (51) |
| Zang et al., 2018 | FIRRE | OGD/R | Mus musculus | Not known | Activate NF-κB signaling | FIRRE and NF-kB form a positive feedback loop to promote transcription of the NLRP3 inflammasome, leading to OGD/R injury in brain microglia. | (52) |
| Cheng et al., 2020 | RMST | OGD/R | Mus musculus | miR-107 | Activate p53/miR-107 signaling | LncRNA RMST-mediated transcription of miR-107 promotes OGD-induced neuronal apoptosis by interacting with hnRNPK | (53) |
| Sun et al., 2019 | RMST | OGD/R | Mus musculus | Not known | Regulate TAK1-NF-κB | RMST competitively interacts with hnRNPK via the TAK1-mediated NF-κB pathway to promote OGD-induced M1 polarization in microglial cells. | (54) |
| Wang et al., 2021a | XIST | OGD/R | Mus musculus | miR-362 | Regulate ROCK2 | Knockout of XIST attenuates neuronal injury and inflammatory responses in cerebral ischemia/reperfusion injury by modulating the miR-362/ROCK2 axis | (55) |
| Wang et al., 2021b | XIST | MCAO | Mus musculus | miR-92a | Regulate Itgα5 and KLF4 | Silencing of LncRNA XIST impairs angiogenesis after ischemic stroke and exacerbates cerebrovascular injury | (56) |
| Wen et al., 2017 | Gm4419 | OGD/R | Mus musculus | Not known | Increase TNF-α, IL-1β, IL-6; Activate NF-κB signaling. | LncRNA Gm4419 promotes OGD/R injury in brain microglia via IκB phosphorylation and NF-κB activation | (57) |