MiR‐139 Inhibits Mcl‐1 Expression and Potentiates TMZ‐Induced Apoptosis in Glioma

Summary Aims Mcl‐1, an antiapoptotic member of the Bcl‐2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro‐RNAs that acted as endogenous sequence‐specific suppressors of gene expression. Methods and results Using computational and TCGA analysis, we identified miR‐139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl‐1 mRNA. Overexpression of miR‐139 led to a clear decrease in Mcl‐1 expression in gliomas. Reporter assays revealed direct post‐transcriptional regulation involving miR‐139 and the 3′‐untranslated region of Mcl‐1. Human glioma tissues with low expression of miR‐139 displayed higher expression of Mcl‐1 protein than those with high expression, suggesting that low miR‐139 contributes to Mcl‐1 overexpression. In addition, upregulation of miR‐139 suppressed the proliferation and enhanced temozolomide (TMZ)‐induced apoptosis. Finally, we observed that Mcl‐1 knockdown resulted in similar effects compared with miR‐139 transfection. Conclusion Our results suggested that miR‐139 negatively regulated Mcl‐1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.