Mechanisms of miR-145 regulating invasion and metastasis of ovarian carcinoma.

MicroRNA-145 (miR-145) can regulate tumor cell invasion, metastasis, apoptosis, proliferation and stem cell differentiation. However, the molecular mechanisms of miR-145 used to regulate ovarian invasion and metastasis remain to be determined. In this study, Transwell cell migration and wound healing assays were used to detect the effects of miR-145 upregulation on ovarian carcinoma cell invasion and metastasis, respectively. The MUC1 expression vector, together with quantitative real-time PCR and Western blotting, was used to investigate the effects of miR-145 on E-cadherin (E-cad)-induced cell invasion and the related molecular mechanisms. The results showed that miR-145 mimics could inhibit SKOV3 cell invasion and metastasis. MiR-145 inhibited mucin 1 (MUC1) post-transcriptional expression by binding to its 3'-untranslated region. The epithelial mesenchymal transition marker E-cad, which is a downstream molecule of MUC1, was promoted by miR-145 overexpression. Furthermore, the E-cad protein level was inversely correlated with MUC1 expression in SKOV3 cells. These observations indicated that promotion of E-cad signaling induced by miR-145 was restrained by MUC1 inhibition. Thus, miR-145 may serve as a tumor suppressor which can downregulate E-cad expression by targeting MUC1, leading to the inhibition of tumor invasion and metastasis. Using miR-145 mimics may be a rational approach for therapeutic applications in ovarian carcinoma in the future.