To investigate the effects of miR-433-3p on the biological behavior of ovarian cancer (OC) cells and the possible molecular mechanisms to provide a new direction for the early diagnosis and treatment of ovarian cancer.

The differential expression of miR-433-3p was identified using bioinformatics analysis and detected in ovarian cancer cell lines by real-time fluorescence quantitative PCR (qPCR). The miR-433-3p mimic, miR-433-3p inhibitor, and negative control groups were transfected into A2780 and SKOV3 cells separately, divided into the following groups: miR-433-3p inhibitor group, inhibitor NC group, miR-433-3p mimic group, and mimic NC group. EdU, colony formation assays, Transwell migration and invasion assays were conducted to assess the effects of miR-433-3p on the biological behavior of ovarian cancer cells. We also evaluated the effect of miR-433-3p on tumor development in mice. Bioinformatics analysis was used to pool the miR-433-3p targets. Dual-luciferase reporter assay, qPCR, and Western blot were used to verify the potential miR-433-3p targets. We also explored the regulation of miR-433-3p in the downstream signaling pathways of target genes.

The miR-433-3p was downregulated in ovarian cancer tissues compared to the normal ovarian tissues. Inhibition of miR-433-3p significantly promoted cell proliferation, migration, invasion, and carboplatin resistance (t values are 4.92, 5.52, 3.02, 3.77, 5.99, 4.03, respectively, all P values <0.05), while miR-433-3p overexpression had the opposite effect (t values are 5.56, 4.15, 2.30, 3.38, 7.69, 2.68, respectively, all P values <0.05). And miR-433-3p suppressed the growth of ovarian cancer xenograft tumors in vivo (t values are 3.78, 2.26, 3.46, 2.65, respectively, all P values <0.05). Moreover, we confirmed that miR-433-3p targeted mitogen-activated protein kinase 8(MAPK8) and growth factor receptor-bound protein 2 (GRB2 )using databases analysis and dual-luciferase reporter assay. We also found that the protein levels of MAPK8 and GRB2 were upregulated in ovarian cancers and had the opposite trend to miR-433-3p. The high MAPK8 or GRB2 levels in ovarian cancer patients were closely associated with poor prognosis. In addition, miR-433-3p could also regulate the critical mediators expression of the MAPK signaling pathway.

The miR-433-3p may inhibit the progression of OC by binding to MAPK8 and GRB2 to regulate the downstream MAPK pathway.

Ovarian cancer; miR-433-3p; Mitogen-activated protein kinase 8; Growth factor receptor-bound protein 2; Mitogen-activated protein kinase signaling pathway