Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway

Abstract

Objective To investigate the apoptosis-inducing effect of sodium valproate (VPA) on nerve cells and the underlying mechanism. Methods Human neuroblastoma SH-SY5Y cells treated with VPA of difterent doses were examined for apoptosis and Mcl-1 protein expression using flow cytometry and Western blotting, respectively. The mRNA expression of Mcl-1 and miR-148a-3p in the treated cells was detected with qRT-PCR, and the promoter activity of Mcl-1 gene was analyzed using a reporter gene assay. The changes of cell apoptosis and Mcl-1 expression in SH-SY5Y cells were analyzed following combined treatment with VPA and a miR-148a-3p antagonist. Results VPA treatment significantly promoted apoptosis and down-regulated Mcl-1 expression at both the mRNA and protein levels in SH-SY5Y cells. VPA treatment did not significantly affect the transcriptional activity of Mcl-1 promoter but up-regulated the expression of miR-148a-3p in SH-SY5Y cells. The application of the miR-148a-3p antagonist obviously attenuated the inhibitory effect of VPA on Mcl-1 expression and VPA-induced apoptosis in the cells. Conclusion VPA promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway.

Keywords

• sodium valproate
• sh-sy5y cells
• mcl-1
• mir-148a-3p
• apoptosis