MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway

Abstract

Xiaowang Guo,1 Xiaoyan Shen,2 Zhijun Yong3 1Department Emergency Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of China; 2Department of Neurology Medicine, The Fourth People’s Hospital of Shaanxi, Xi’an City, Shaanxi Province, 710000, People’s Republic of China; 3Department of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaCorrespondence: Zhijun YongDepartment of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaEmail [email protected]: Ischemic stroke is a devastating disease with very limited therapeutics. Although miR-101 has been reported to play crucial roles in various human diseases, its role in ischemic stroke remains unclear.Methods: Ischemia-reperfusion (I/R) injury neuronal cells and rat model with I/R injury were constructed. Viability and apoptosis of I/R model cells with miR-101 overexpression or downregulation were evaluated. Potential targets of miR-101 were predicted using miRNA database microRNA.org and confirmed using luciferase reporter assays. Meanwhile, JAK2 and p-STAT3 protein levels were evaluated by Western blot. In addition, rescue experiments (silencing of JAK2) were applied to determine the role of miR-101 in cerebral I/R injury.Results: MiR-101 was significantly downregulated in OGD/R-induced neuronal cells and brain tissues with I/R injury. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited apoptosis of OGD/R-induced neuronal cells in vitro and efficiently protected rats from ischemic brain injury in vivo. By contrast, miR-101 inhibitor exacerbated growth defect, apoptosis, and ischemic brain injury. Luciferase reporter assay indicated that JAK2 was a direct target of mIR-101, and JAK2 silencing effectively reversed the miR-101 inhibitor-induced neuronal cell apoptosis in vitro and reduced cerebral infarction volume in vivo.Conclusion: Our study demonstrated that miR-101 efficiently protected neuronal cells from apoptosis and ischemic brain injury through regulating the JAK2/STAT3 signaling pathway, suggesting that miR-101 might be a potential target for treatment of ischemic stroke.Keywords: ischemic stroke, miR-101, JAK2/STAT3 signaling

Keywords

• ischemic stroke
• mir-101
• jak2/stat3 signaling