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 (MALAT1) or miR-200 family members were shown to facilitate EMT in multiple human cancers, but the regulatory mechanism by which MALAT1 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 MALAT1 levels were lower. Moreover, we found that miR-200c bound directly to MALAT1 using luciferase reporter and qRT-PCR assays. MALAT1 and miR-200c are reciprocally repressed, and TGF-β increased MALAT1 expression by inhibiting miR-200c. When the interaction between miR-200c/MALAT1 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/MALAT1 axis is a target with therapeutic potential in EEC. However, different expression model of miR-200c and MALAT1 in EEC with that in other organ carcinomas needs further mechanism researches.
Keywords: Endometrioid endometrial carcinoma; Invasion; MALAT1; miR-200c.
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