MicroRNA-760 Inhibits Doxorubicin Resistance in Hepatocellular Carcinoma through Regulating Notch1/Hes1-PTEN/Akt Signaling Pathway

Abstract

Accumulating studies have suggested that microRNA-760 (miR-760) plays an important role in chemoresistance of various cancer cells. However, whether miR-760 regulates the chemoresistance of hepatocellular carcinoma (HCC) remains unclear. In this study, we found that miR-760 was decreased in HCC cell lines, and doxorubicin (Dox) treatment significantly decreased miR-760 expression in HCC cells. Overexpression of miR-760 sensitized HCC cells to Dox-induced cytotoxicity and apoptosis, whereas miR-760 inhibition showed the opposite effects. Notch1 was predicted as a target gene of miR-760. miR-760 negatively regulated Notch1 expression and Notch1/Hes1 signaling. Overexpression of miR-760 increased PTEN expression and decreased the phosphorylation of Akt. Activation of Notch signaling significantly reversed the inhibitory effect of miR-760 on Dox-resistance and abrogated the effect of miR-760 on the PTEN/Akt signaling pathway in HCC cells. Overall, our results demonstrate that miR-760 inhibits Dox-resistance in HCC cells through inhibiting Notch1 and promoting PTEN expression.

Keywords: Hepatocellular Carcinoma; Notch1; PTEN; miR-760.