MicroRNA-181 Functions as an Antioncogene and Mediates NF-κB Pathway by Targeting RTKN2 in Ovarian Cancers

MicroRNA (miR)-181 has been reported to participate in carcinogenesis and tumor progression in several malignant cancers, but its expression and biological functions in ovarian cancer have remained largely unclarified. Here, we first measured miR-181 expression in clinical ovarian cancers and found the expression levels of miR-181 were significantly lower in ovarian cancer tissues than that in adjacent tissues. Next, we screened and identified a direct miR-181 target, Rhotekin2 (RTKN2). A correlation between miR-181 and RTKN2 expression was also confirmed in clinical samples of ovarian cancers. Upregulation of miR-181 would specifically and markedly suppress RTKN2 expression. The miR-181-overexpressing subclones showed significant cell growth inhibition by cell apoptosis induction and significant impairment of cell invasiveness in SKOV3 and HO8910 ovarian cancer cells. To identify the mechanisms, we investigated the NF-kappa B pathway and found that nuclear factor-kappa B (NF-kappa B), B-cell lymphoma-2 (Bcl-2), and vascular endothelial growth factor (VEGF) were suppressed, whereas I kappa B alpha was promoted in miR-181-overexpressing cells. These findings indicate that miR-181 functions as a tumor suppressor and plays a substantial role in inhibiting the tumorigenesis and reversing the metastasis of ovarian cancer through RTKN2-NF-kappa B signaling pathway in vitro. Taken together, we believe that miR-181 may be a promising therapeutic target for treating malignant ovarian cancers.