Journal
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
Volume 37, Issue 6, Pages 468-478Publisher
WILEY
DOI: 10.1002/kjm2.12362
Keywords
ATG3; cerebral ischemia– reperfusion injury; JAK2; STAT3pathway; lncRNA RMRP; microRNA‐ 613
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Funding
- China's 13th Five-Year key RESEARCH and development projects [2016YFC1300700]
- National key RESEARCH and development projects during the 13th Five-Year Plan period [:2016YFC13015012]
- 13th Five-Year Plan for key RESEARCH and development major chronic non-communicable disease prevention and control special project [2016YFC1301502]
- Major Science and Technology Project of Changzhou Municipal Health Commission [ZD202005]
- Young Talent Science and Technology Project of Changzhou Municipal Health Committee [QN202024]
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This study investigated the role of lncRNA RMRP in cerebral I/R injury, revealing that RMRP upregulates ATG3 expression through miR-613 and inhibits the JAK2/STAT3 pathway activation, ultimately promoting cerebral I/R injury in mice.
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.
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