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Long non-coding RNA Gm11974 aggravates oxygen–glucose deprivation-induced injury via miR-122-5p/SEMA3A axis in ischaemic stroke

Abstract

Long non-coding RNAs (lncRNAs) play important roles in ischaemic stroke. This study aimed to investigate the role and potential mechanism of lncRNA Gm11974 in ischaemic stroke. Mouse neuroblastoma N2a cells were treated with oxygen–glucose deprivation (OGD). The levels of Gm11974, microRNA-122-5p (miR-122-5p) and semaphorin 3A (SEMA3A) were detected by quantitative real-time PCR (qRT-PCR) or western blot. Cell viability and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Caspase-3 Assay Kit and flow Cytometry. The levels of oxidative stress indicators were measured by using commercial kits. The relationship between miR-122-5p and Gm11974 or SEMA3A was verified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Middle cerebral artery occlusion (MCAO) in mice was used to mimic ischaemic stroke. Gm11974 and SEMA3A were up-regulated, while miR-122-5p was down-regulated in OGD-treated N2a cells and MCAO mice. Down-regulation of Gm11974 ameliorated OGD-mediated N2a cell damage by increasing cell viability and reducing cell apoptosis and oxidative stress. Gm11974 promoted OGD-induced injury in N2a cells via negatively regulating miR-122-5p. Also, miR-122-5p alleviated OGD-resulted N2a cell injury by targeting SEMA3A. Moreover, silencing of Gm11974 decreased infarct volume and neurological score in MCAO mice. Knockdown of Gm11974 attenuated neuronal injury in ischaemic stroke by regulating miR-122-5p/SEMA3A signaling pathway.

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Correspondence to Ping Liu.

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Yang, L., Wang, L., Wang, J. et al. Long non-coding RNA Gm11974 aggravates oxygen–glucose deprivation-induced injury via miR-122-5p/SEMA3A axis in ischaemic stroke. Metab Brain Dis 36, 2059–2069 (2021). https://doi.org/10.1007/s11011-021-00792-7

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Keywords

  • Ischemic stroke
  • Gm11974
  • miR-122-5p
  • SEMA3A
  • OGD