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miR-187-3p inhibitor attenuates cerebral ischemia/reperfusion injury by regulating Seipin-mediated autophagic flux

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 investigate...

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Detalles Bibliográficos
Autores principales: Ren, Zhenkui, Xie, Peng, Lv, Ju, Hu, Yumei, Guan, Zhizhong, Chen, Ling, Yu, Wenfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387098/
https://www.ncbi.nlm.nih.gov/pubmed/32705147
http://dx.doi.org/10.3892/ijmm.2020.4642
Descripción
Sumario: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.