Abstract
The role of microRNA-18a (miRNA/miR-18a) as a tumor suppressor or promoter in a number of different types of cancer has been reported. However, to date, the expression and the effects of miR-18a in epithelial ovarian cancer (EOC) remain elusive. In the present study, the expression of miR-18a in patient EOC tissues and ovarian cancer cell lines was investigated using the reverse transcription-quantitative polymerase chain reaction. Luciferase assays and western blotting were performed to detect the potential direct targets of miR-18a. An A2780cp intraperitoneal mouse model, and Cell Counting Kit 8, flow cytometry and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays, were used to investigate the effect of miR-18a on tumor growth in vivo and in vitro. The results indicated that the expression of miR-18a was reduced in EOC tissue and in the investigated ovarian cancer cell lines compared with non-malignant (normal) ovarian tissues and the human ovarian epithelium cell line, respectively. Overexpression of miR-18a in the A2780s and A2780cp cell lines significantly induced cell cycle arrest and apoptosis. It was demonstrated that miR-18a directly targets tumor protein p53-regulating inhibitor of apoptosis gene 1 and inositol phosphate multikinase, hence regulating the expression of downstream targets. The A2780cp intraperitoneal mouse model was employed and the results indicated that miR-18a may inhibit A2780cp intraperitoneal tumor growth in vivo by inhibiting proliferation and inducing apoptosis. Together, the results of the present study demonstrated that miR-18a has a role as a tumor suppressor by inhibiting proliferation and inducing apoptosis. Assessment of miR-18a expression may provide a novel method for diagnosis and be a therapeutic target for EOC.