MicroRNA‐221 targeting PI3‐K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma

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Abstract
MicroRNAs (miRNAs) are short regulatory RNAs that negatively regulate protein biosynthesis at the post‐transcriptional level and participate in the pathogenesis of different types of human cancers, including glioblastoma. In particular, the levels of miRNA‐221 are overexpressed in many cancers and miRNA‐221 exerts its functions as an oncogene. Nevertheless, the roles of miRNA‐221 in carmustine (BCNU)‐resistant glioma cells have not been totally elucidated. In the present study, we explored the effects of miRNA‐221 on BCNU‐resistant glioma cells and the possible molecular mechanisms by which miRNA‐221 mediated the cell proliferation, survival, apoptosis and BCNU resistance were investigated. We found that miR‐221 was overexpressed in glioma cells, including BCNU‐resistant cells. Moreover, we found that miR‐221 regulated cell proliferation and BCNU resistance in glioma cells. Overexpression of miR‐221 led to cell survival and BCNU resistance and reduced cell apoptosis induced by BCNU, whereas knockdown of miR‐221 inhibited cell proliferation and prompted BCNU sensitivity and cell apoptosis. Further investigation revealed that miR‐221 down‐regulated PTEN and activated Akt, which resulted in cell survival and BCNU resistance. Overexpression of PTEN lacking 3′UTR or PI3‐K/Akt specific inhibitor wortmannin attenuated miR‐221‐mediated BCNU resistance and prompted cell apoptosis. We propose that miR‐221 regulated cell proliferation and BCNU resistance in glioma cells by targeting PI3‐K/PTEN/Akt signaling axis. Our findings may provide a new potential therapeutic target for treatment of glioblastoma.

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