GAS5 knockdown ameliorates apoptosis and inflammatory response by modulating miR-26b-5p/Smad1 axis in cerebral ischaemia/reperfusion injury.

Ischemic stroke (IS) caused by cerebral arterial embolism remains the leading cause of disability and death worldwide. Cerebral ischemia / reperfusion (CI / R) injury is one of the common complications of ischemic stroke. Growth arrest specific transcript 5 (GAS5) has been found to be abnormally expressed in various tumors. However, the role and potential molecular mechanisms of GAS5 in CI / R-induced injury remain unknown. This study established a CI / R injury model in vivo and in vitro. The results showed that the expression of GAS5 was increased in CI / R rats, while miR-26b-5p expression was decreased. Besides, knockdown of GAS5 by siRNA (si-GAS5) reversed CI / R-induced apoptosis and inflammatory responses. Notably, bioinformatics analysis indicated that GAS5 competitively adsorbed miR-26b-5p, and the relationship was further confirmed by pull-down assay. In addition, miR-26b-5p overexpression reversed CI / R-induced apoptosis and inflammatory responses, whereas low expression of miR-26b-5p had the opposite effect. Moreover, TargetScan assay predicted that drosophila mothers against decapentaplegic protein 1 (Smad1) was a target of miR-26b-5p, and miR-26b-5p overexpression inhibited Smad1 expression. Conversely, Smad1 overexpression reversed the inhibitory effect of miR-26b-5p on CI / R-induced apoptosis and inflammatory responses in rats. Collectively, these results indicate that GAS5 knockdown can improve apoptosis and inflammatory responses by modulating the miR-26b-5p / Smad1 axis in CI / R rats.