Knockdown of long non-coding RNA RMRP protects cerebral ischemia-reperfusion injury via the microRNA-613/ATG3 axis and the JAK2/STAT3 pathway.

Cerebral ischemia-reperfusion (I/R) injury can induce the mitophagy of neurons in the ischemic brain. Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of various injuries, especially in cerebral I/R injury. The purpose of this study is to investigate the molecular mechanism of lncRNA RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in cerebral I/R injury. The middle cerebral artery occlusion (MCAO) mouse model was established. Neurological deficit score, pathological structure, infarcted area, neuron number, cell apoptosis, and coagulation ability of MCAO mice were evaluated. The expressions of RMRP, microRNA (miR)-613, and ATG3 in MCAO mice were detected. The binding relationships among miR-613, RMRP, and ATG3 were predicted and verified. Neuro 2A (N2a) cells were treated with oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury. Cell viability and apoptosis assays were performed. The effects of miR-613, ATG3, and RMRP on I/R injury were verified by functional rescue experiments. JAK2/STAT3 phosphorylation level was detected. We found significantly upregulated RMRP and ATG3, and downregulated miR-613 expressions in MCAO mice. RMRP could escalate ATG3 mRNA expression through miR-613. RMRP knockdown promoted viability and inhibited apoptosis of OGD/R-treated N2a cells, which could be reversed by miR-613 inhibition or ATG3 overexpression. RMRP overexpression inhibited the activation of JAK2/STAT3 signaling pathway. We demonstrated that lncRNA RMRP competitively bound to miR-613, leading to the increase of ATG3 expression and the inhibition the JAK2/STAT3 pathway, thus promoting cerebral I/R injury in mice. © 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.

Citation

Li Wei, Ya Peng, Xiao-Jun Yang, Peng Zhou. Knockdown of long non-coding RNA RMRP protects cerebral ischemia-reperfusion injury via the microRNA-613/ATG3 axis and the JAK2/STAT3 pathway. The Kaohsiung journal of medical sciences. 2021 Jun;37(6):468-478

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PMID: 33560543

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