MiR?187?3p inhibitor attenuates cerebral ischemia/reperfusion injury by regulating Seipin?mediated autophagic flux.

ABSTRACT: MicroRNAs (miRNAs/miRs) have been reported to affect ischemia/reperfusion (I/R)?induced cerebral damage. miRNAs cause post?transcriptional gene silencing by binding to the protein?coding sequence (CDS) of mRNAs. Seipin has a potential role in regulating autophagic flux. The present study investigated the involvement of miR?187?3p in Seipin expression, autophagic flux and apoptosis in vitro, as well as the underlying mechanism, using PC12 cells exposed to oxygen?glucose deprivation/reoxygenation (OGD/R), which mimicked the process of I/R. In comparison with control PC12 cells, OGD/R caused an increase in the level of miR?187?3p and a decrease in Seipin protein levels without changes in the level of Seipin mRNA. Using bioinformatics analysis, it was identified that miR?187?3p could bind to the CDS of Seipin. miR?187?3p inhibitor attenuated the reduction in Seipin protein expression in OGD/R?treated PC12 cells. Following OGD/R, autophagic flux was reduced and apoptosis was enhanced, which were attenuated by inhibition of miR?187?3p. Compared with OGD/R?treated PC12 cells, Seipin knockdown further impaired autophagic flux and promoted neuronal apoptosis, which were insensitive to inhibition of miR?187?3p. Furthermore, treatment with miR?187?3p inhibitor could decrease the infarction volume in a rat model of middle cerebral artery occlusion/reperfusion. The present findings indicated that miR?187?3p inhibitor attenuated ischemia?induced cerebral damage by rescuing Seipin expression to improve autophagic flux.

SUBMITTER: Ren Z 

PROVIDER: S-EPMC7387098 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature