Long noncoding RNA XIST enhances cerebral ischemia-reperfusion injury by regulating miR-486-5p and GAB2.

F Xiong, W-P Wei, Y-B Liu, Y Wang, H-Y Zhang, R Liu

European review for medical and pharmacological sciences 2021 Feb

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LncRNA XIST has been reported to act as diverse function in different human diseases. Our study is designed to detect the role of lncRNA XIST and the regulatory mechanisms of XIST/miR-486-5p/GAB2 in cerebral I/R injury. In our article, SH-SY5Y cells were treated with oxygen-glucose deprivation reperfusion (OGDR) to mimic I/R injury. RT-qPCR assay was performed to detect the mRNA expression of XIST, GAB2 and miR-486-5p. The correlation between XIST and miR-486-5p, miR-486-5p and GAB2 were verified by RT-qPCR assay and Dual-Luciferase reporter assay. MTT assay was used to detect cell viability of SH-SY5Y cells treated with I/R. The protein expression of GAB2, apoptosis-related proteins (Bax/Bcl-2) were explored by Western blot assay. XIST and GAB2 were significantly highly expressed, while miR-486-5p was low expressed in SH-SY5Y cells under I/R. XIST exacerbated the oxidative damage of I/R cells. Moreover, XIST was found to restrain cell viability and induce cell apoptosis. For our experiment, miR-486-5p was a target of XIST, and GAB2 was a downstream gene of miR-486-5p. Furthermore, miR-486-5p mimic promoted cell proliferation and inhibited cell apoptosis, while XIST co-transfection reversed the effect of miR-486-5p. In addition, XIST was found to impair the inhibitory effect of miR-486-5p on expression of GAB2 in I/R cells. Our results indicated that XIST promoted cerebral I/R injury via modulating miR-486-5p and GAB2.

Citation

F Xiong, W-P Wei, Y-B Liu, Y Wang, H-Y Zhang, R Liu. Long noncoding RNA XIST enhances cerebral ischemia-reperfusion injury by regulating miR-486-5p and GAB2. European review for medical and pharmacological sciences. 2021 Feb;25(4):2013-2020