Increased miR‑187‑3p expression after cerebral ischemia/reperfusion induces apoptosis via initiation of endoplasmic reticulum stress

Neurosci Lett. 2021 Aug 10:759:135947. doi: 10.1016/j.neulet.2021.135947. Epub 2021 May 17.


Ischemia/reperfusion (I/R) injury induces activation of the endoplasmic reticulum stress (ERS) pathway, accompanied by an increase in apoptosis. Multiple microRNAs (miRNAs/miRs) are dysregulated during I/R and contribute to I/R-induced injury. miRNAs act as suppressors of gene expression and negatively regulate gene expression by targeting the protein-coding sequence (CDS) of specific target mRNAs. Seipin is an endoplasmic reticulum protein that has recently been associated with ERS. We previously reported that seipin is the target gene of miR‑187‑3p. Therefore, we explored the involvement of miR-187-3p in I/R-induced ERS via the regulation of seipin. A rat MCAO/R model was established by 1 h of occlusion and 24 h reperfusion. Neurological deficits and infarction area were examined. PC12 cells were exposed to oxygen‑glucose deprivation/reoxygenation (OGD/R) to model I/R. Expression levels of miR-187-3p and proteins related to ERS and apoptosis were measured using RT-PCR, western blotting, immunofluorescence, and immunohistochemistry, respectively. TUNEL staining was used to assay apoptosis. MCAO/R-induced morphological changes were analyzed with Nissl staining and Hematoxylin-eosin staining. I/R-induced ERS was closely associated with an increase in miR-1873p and a decrease in seipin expression. miR-187-3p agomir further activated the ERS pathway and promoted apoptosis but decreased seipin expression levels; these effects were reversed by miR-187-3p antagomir. Moreover, seipin knockdown aggravated ERS in PC12 cells after OGD/R, and this change was rescued by seipin overexpression. miR-187-3p antagomir did not suppress ERS and apoptosis in seipin knockdown PC12 cells after OGD/R. Our findings demonstrate that the inhibition of miR‑187‑3p attenuated I/R‑induced cerebral injury by regulating seipin-mediated ERS.

Keywords: Cerebral ischemia; Endoplasmic reticulum stress; GRP78; Seipin; miR-187-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Brain Ischemia / metabolism*
  • Endoplasmic Reticulum Stress / physiology*
  • GTP-Binding Protein gamma Subunits / metabolism
  • MicroRNAs / metabolism*
  • PC12 Cells
  • Rats
  • Reperfusion Injury / metabolism*


  • GTP-Binding Protein gamma Subunits
  • MIRN187 microRNA, rat
  • MicroRNAs