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

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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.

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Author notes

  1. Zhongquan Yi and Yuanyuan Shi contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Central Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, West Xindu Road 2#, Yancheng, 224001, Jiangsu, People’s Republic of China

    Zhongquan Yi, Yuanyuan Shi, Panwen Zhao & Pinglei Pan

  2. Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321#, Nanjing, 210008, Jiangsu, People’s Republic of China

    Yun Xu

  3. Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, West Xindu Road 2#, Yancheng, 224001, Jiangsu, People’s Republic of China

    Pinglei Pan

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  1. Zhongquan Yi
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Yi, Z., Shi, Y., Zhao, P. et al. Overexpression of miR-217-5p protects against oxygen–glucose deprivation/reperfusion-induced neuronal injury via inhibition of PTEN. Human Cell 33, 1026–1035 (2020). https://doi.org/10.1007/s13577-020-00396-w

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