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MiR-7-5p enhances cerebral ischemia-reperfusion injury by degrading sirt1 mRNA.
Journal of Cardiovascular Pharmacology 2020 May 19
Cerebral ischemia-reperfusion (I/R) is a kind of neurovascular disease that causes serious cerebral damage. MicroRNAs (miRNAs) have been widely reported to participate in multiple diseases including cerebral ischemia-reperfusion (I/R) injury. However, the exact mechanisms of miR-7-5p in cerebral I/R injury was not fully elucidated. In this study, we explored the biological role and regulatory mechanism of miR-7-5p in cerebral I/R injury. We established an in vivo model of cerebral I/R by middle cerebral artery occlusion (MCAO) and an in vitro cellular model of cerebral I/R injury through treating neurons (SH-SY5Y cells) with oxygen-glucose deprivation (OGD). In addition, miR-7-5p expression was confirmed to be up-regulated in cerebral I/R rat model and OGD/R treated SH-SY5Y cells. Moreover, miR-7-5p inhibition overtly suppressed cerebral injury, cerebral inflammation and SH-SY5Y cells apoptosis. Sirtuin 1 (sirt1) is previously reported to alleviate I/R and in this study, it was identified to be a target of miR-7-5p based on luciferase reporter assay. RT-qPCR revealed sirt1 expression was down-regulated in cerebral I/R rat model and OGD/R treated SH-SY5Y cells. Besides, miR-7-5p negatively regulated sirt1. Finally, rescue assays delineated sirt1 overexpression recovered the miR-7-5p up-regulation-induced promotion on cerebral I/R injury. In conclusion, miR-7-5p enhanced cerebral I/R injury by degrading sirt1, providing a new paradigm to investigate cerebral I/R injury.
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