LncRNA NEAT1 stabilized Wnt3a via U2AF2 and activated Wnt/β-catenin pathway to alleviate ischemia stroke induced injury

Abstract

BackgroundIschaemic stroke is the leading cause of mortality and disability in the world. LncRNA NEAT1 has been shown to play an important role in ischaemic injury, but the molecular mechanism remains unclear. MethodsqRT–PCR was used to determine the expression of lncRNA NEAT1 in OGD/R-induced BV-2 cells. Cell viability was assessed by an MTT assay, and cell apoptosis was assessed by flow cytometry. The expression of related proteins was evaluated by Western blotting and ELISA. The interactions among lncRNA NEAT1, U2AF2 and Wnt3a mRNA was demonstrated by RIP and RNA pulldown assays. XAV-939 was used as an inhibitor of the Wnt/β-catenin pathway. ResultsLncRNA NEAT1 was found to be downregulated in OGD/R-induced BV-2 cells. Overexpression of lncRNA NEAT1 protected BV-2 cells against OGD/R-induced injury. LncRNA NEAT1 enhanced the stability of Wnt3a mRNA via U2AF2. Knockdown of Wnt3a or blockade of the Wnt/β-catenin pathway rescued the effect of lncRNA NEAT1. ConclusionsLncRNA NEAT1 protected cells against OGD/R-induced apoptosis and the inflammatory response by activating the Wnt/β-catenin pathway through upregulation of Wnt3a in a U2AF2-dependent manner. LncRNA NEAT1 could be a promising therapeutic candidate for ischaemic stroke treatment in the future.