Overexpression of microRNA-145 enhanced docetaxel sensitivity in breast cancer cells via inactivation of protein kinase B gamma-mediated phosphoinositide 3-kinase -protein kinase B pathway.

ABSTRACT: Chemoresistance is a major challenge for the treatment of breast cancer (BC). Previous studies showed that miR-145 level decreases in chemoresistant BC tissues. Nevertheless, the biological function of miR-145 on docetaxel resistance of BC cells remains unclear, which is what our research attempted to clarify. RT-qPCR analyzed miR-145 level, and cell viability and colony formation assays assessed the impact of miR-145 on docetaxel resistance. Molecular mechanisms of miR-145-mediated docetaxel sensitivity were examined by Luciferase reporter assay and Western Blot assessed the function of AKT3 and PI3K/AKT signaling. Our research found that miR-145 expression presented significant downregulation in docetaxel-resistant BC cells. Meanwhile, miR-145 overexpression facilitated the docetaxel sensitivity of BC cells in vivo and in vitro, while the miR-145 inhibitor decreased the sensitivity of BC cells to docetaxel. We also observed that miR-145 inhibited docetaxel resistance mainly via downregulation of the AKT3 expression and further inhibited PI3K/AKT pathway. To conclude, this research provides a novel strategy for improving chemosensitivity through the newly identified miR-145-AKT3/PI3K-AKT signaling pathway in BC.

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC9278436 | biostudies-literature |

REPOSITORIES: biostudies-literature