MicroRNA-654-3p enhances cisplatin sensitivity by targeting QPRT and inhibiting the PI3K/AKT signaling pathway in ovarian cancer cells.

ABSTRACT

Dysregulation of microRNAs serves a crucial role in the chemosensitivity to cisplatin (DDP) in ovarian cancer (OVC). The abnormal expression of microRNA (miR)-654-3p has been reported in several types of human cancer. However, the association between miR-654-3p and cisplatin resistance in human OVC remains unclear. The present study aimed to investigate the role and mechanism of miR-654-3p in DDP resistance in OVC. The results demonstrated that miR-654-3p was significantly downregulated in ovarian cancer tissues and cells, as well as DDP-resistant IGROV-1/DDP cells, compared with adjacent non-tumoral tissue and IOSE386 cells. Overexpression of miR-654-3p significantly suppressed the proliferation and migration of ovarian cancer cells and increased the sensitivity of IGROV-1/DDP cells to DDP. Luciferase reporter assay demonstrated that quinolinate phosphoribosyl transferase (QPRT) was a target of miR-654-3p; overexpression of miR-654-3p inhibited QPRT expression by binding to the 3'-untranslated region of QPRT. In addition, inhibition of miR-654-3p reversed the suppressive effects of QPRT-targeting short interfering RNA on the proliferation and chemoresistance of ovarian cancer cells. Therefore, the results of the present study revealed a previously unrecognized regulatory mechanism that miR-654-3p enhances DDP sensitivity of OVC cells by downregulating QPRT expression; in addition, the present study highlighted the therapeutic implications of miR-654-3p upregulation in OVC.