lncRNA WT1-AS attenuates hypoxia/ischemiainduced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis.

Autor: Jianquan You, Fei Qian, Yu Huang, Yingxuan Guo, Yaqian Lv, Yuqi Yang, Xiupan Lu, Ting Guo, Jun Wang, Bin Gu
Zdroj: Open Medicine; Jan2022, Vol. 17 Issue 1, p1338-1349, 12p, 2 Charts, 7 Graphs
Abstrakt: This study aimed to investigate the role and mechanism of long non-coding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in cerebral ischemic stroke. The Starbase database and dual-luciferase reporter gene assay were used to analyze the interaction between lncRNA WT1 antisense RNA (lncRNA WT1-AS) and microRNA-186-5p (miR-186-5p). Reverse transcription-quantitative PCR analysis was performed to determine lncRNA WT1-AS and miR-186-5p levels. An oxygen glucose deprivation (OGD)- induced SH-SY5Y cell injury model was established. Cell viability and apoptosis were determined using 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and flow cytometric assays, respectively. Caspase 3 activity was evaluated using a caspase 3 activity detection kit. The results showed that miR-186-5p is a direct target of the lncRNA WT1-AS. In addition, lncRNA WT1-AS levels were downregulated and miR-186-5p levels were upregulated in the blood samples of patients with ischemic stroke and OGD-induced SH-SY5Y cells. WT1-AS overexpression promoted OGD-induced cell viability and reduced the cell apoptosis and caspase 3 activity. However, these effects were reversed by miR-186-5p overexpression. Furthermore, the results demonstrated that the X-linked inhibitor of apoptosis (XIAP) was directly targeted by miR-186-5p. Similarly, transfection with the miR-186-5p inhibitor reduced OGDinduced neuronal damage by upregulating XIAP expression. In conclusion, lncRNA WT1-AS attenuates hypoxia/ischemiainduced neuronal injury in cerebral ischemic stroke through the miR-186-5p/XIAP axis. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index