MiRNA-409-3p enhances cisplatin-sensitivity of ovarian cancer cells by blocking the autophagy mediated by Fip200

Efficacy of chemotherapy for ovarian cancer (OC) is usually affected by various factors,especially the chemoresistance of ovarian cancer cells. Downregulation of miR-409-3p has been found in a variety of tumors. However, the role of miR-409-3p in chemo-resistant OC cells still remains unknown. The aim of this study was to investigate the effect of miR-409-3p on cisplatin-resistant OC cells and to elucidate the mechanism by which enhances cisplatin-sensitivity of OC cells. Expression of miR-409-3p in OC cells was assessed by qRT-PCR. MTS and clone formation assays were used to validate cell proliferation. Flow cytometry was performed for apoptosis analysis. Western blot assay was used to assess the alterations of signaling pathway related proteins. BALB/c nude mouse xenograft model was used to evaluate the role of miR-409-3p in cisplatin-resistant OC cells in vivo. We found that miR-409-3p was apparently downregulated in the OC cells compared with normal ovarian cells. Results also showed that compared with the cisplatinsensitive cells, in cisplatin-resistant cells, miR-409-3p was decreased with an obvious increasing autophagic activity. In addition, based on the bioinformatics analysis, miR-409-3p was supposed to bind with Fip200. Our results demonstrated that in miR-409-3p overexpression cells, significant decreases were seen in protein expression of Fip200 and autophagic activity, which might be caused by conjugation between overexpressed miR-409-3p and 3'-UTR in Fip200 mRNA. Moreover, under the miR-409-3p overexpression, we found that cisplatin-sensitive and cisplatin-resistant ovarian cancer cells were more sensitive to the chemotherapeutics, which could be reversed by Fip2000. Further, we found that chemosensitivity in tumor cells was augmented by miR-409-3p overexpression, and Fip200 acted as a key link in interrupting the chemotherapy-induced autophagy. Results mentioned above revealed that miR-409-3p can ameliorate cisplatin-sensitivity of ovarian cancer cells through blocking the autophagy mediated by Fip200.