MicroRNA-27a regulates the proliferation, chemosensitivity and invasion of human ovarian cancer cell lines by targeting Cullin 5

Abstract

Reports suggest that microRNAs have implications in the development of several diseases including cancer. It is therefore believed that miRs may act as therapeutic targets for cancer treatment. The treatment of ovarian cancer is mainly obstructed by lack of biomarkers and efficient drug targets. Against this backdrop, this study was undertaken to unveil the therapeutic implications of miR-27a in ovarian cancer. The results showed that the expression of miR-27a was significantly elevated in ovarian cancer tissues and cell lines. Inhibition of miR-27a expression resulted in the decrease of proliferation rate and colony formation potential of the SK-OV-3 and OVACAR-3 cells via G₂/M arrest. The miR-27a inhibition triggered G₂/M arrest of SK-OV-3 and OVACAR-3 cells was accompanied with depletion of cyclin A and B1 expression levels. TargetScan analysis together with dual reporter assay revealed that miR-27a exerts its effects via modulation of CUL5 expression. The CUL5 was shown to be suppressed in the ovarian cancer tissues and cell lines and suppression of miR-27a expression caused upregulation of CUL5 expression. Overexpression of CUL5 caused inhibition of SK-OV-3 and OVACAR-3 cell proliferation via induction of G₂/M arrest, similar to that of miR-27a inhibition. Interestingly, CUL5 overexpression reversed the effects of miR-27a inhibition on the viability of SK-OV-3 cells. Finally, the suppression of miR-27a could enhance the chemosensitivity of the SK-OV-3 cells to cisplatin and docetaxel anticancer drugs and also decreased their migration and invasion. The findings of this study revealed that miR-27a suppression inhibits the growth, chemosensitivity and invasion of ovarian cancer and may prove beneficial in the ovarian cancer management.

Keywords: Cell cycle arrest; Invasion; MicroRNA; Ovarian cancer; Proliferation.