Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma

摘要

Endometrioid endometrial carcinoma (EEC) is the most common gynecologic malignancy around the world. Epithelial-to-mesenchymal transition (EMT) is a core process during EEC cell invasion. The abnormal expression of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALATI) or miR-200 family members were shown to facilitate EMT in multiple human cancers, but the regulatory mechanism by which MALATI and miR-200 act remains unknown. Previous studies have shown that miR-200 family members are enriched in EEC as well as melanoma and some ovarian carcinomas. In the present study, we first showed that miR-200c levels were higher in most EEC specimens than in non-tumor tissues, while MALATI levels were lower. Moreover, we found that miR-200c bound directly to MALATI using luciferase reporter and qRT-PCR assays. MALATI and miR-200c are reciprocally repressed, and TGF-beta increased MALATI expression by inhibiting miR-200c. When the interaction between miR-200c/MALATI was interrupted, the invasive capacity of EEC cells was decreased and EMT markers expression were altered in vitro. A xenograft tumor model was used to show that targeting the miR-200c/MALAT1 axis inhibited EEC growth and EMT-associated protein expression in vivo. In summary, miR-200c/MALATI axis is a target with therapeutic potential in EEC. However, different expression model of miR-200c and MALATI in EEC with that in other organ carcinomas needs further mechanism researches. (C) 2016 Elsevier Ireland Ltd. All rights reserved.