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Overexpression of miR-217-5p protects against oxygen-glucose deprivation/reperfusion-induced neuronal injury via inhibition of PTEN.

Abstract
Ischemic stroke is characterized by loss of brain function because of cerebral ischemia. Evidence has been shown that miR-217-5p is significantly downregulated in infarcted brain areas following focal cerebral ischemia. However, the role of miR-217-5p in ischemic stroke is still unclear. To mimic ischemia/reperfusion (I/R) injury conditions in vitro, SH-SY5Y cells were treated with oxygen-glucose deprivation/reperfusion (OGD/R). Our data found that PTEN was the directly target of miR-217-5p in SH-SY5Y cells. The level of miR-217-5p was significantly decreased, while the level of PTEN was notably increased in SH-SY5Y cells following OGD/R treatment. Overexpression of miR-217-5p markedly promoted the proliferation and cell cycle progression, and inhibited apoptosis in OGD/R-treated SH-SY5Y cells. In addition, overexpression of miR-217-5p significantly decreased the expressions of PTEN and FOXO1, but increased the expression of p-Akt in OGD/R-treated SH-SY5Y cells. Moreover, methylation specific PCR (MSP) results indicated the CpG islands in the promoter region of miR-217-5p were hypermethylated in SH-SY5Y cells under OGD/R. Meanwhile, the DNA methylation of miR-217-5p promoter region decreased expression of miR-217-5p. Our data indicated that miR-217-5p could attenuate ischemic injury by inhibiting PTEN. In addition, DNA methylation-mediated silencing of miR-217-5p may serve as a promising therapeutic target of ischemic stroke.
AuthorsZhongquan Yi, Yuanyuan Shi, Panwen Zhao, Yun Xu, Pinglei Pan
JournalHuman cell (Hum Cell) Vol. 33 Issue 4 Pg. 1026-1035 (Oct 2020) ISSN: 1749-0774 [Electronic] Japan
PMID32683553 (Publication Type: Journal Article)
Chemical References
  • MIRN217 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Glucose
  • Oxygen
Topics
  • Cells, Cultured
  • DNA Methylation
  • Gene Expression (genetics)
  • Glucose (metabolism)
  • Humans
  • MicroRNAs (genetics, metabolism, physiology)
  • Molecular Targeted Therapy
  • Neurons (pathology)
  • Oxygen (metabolism)
  • PTEN Phosphohydrolase (genetics, metabolism)
  • Reperfusion Injury (etiology, genetics, therapy)
  • Up-Regulation (genetics)

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