OncoTargets and Therapy (Nov 2019)
miR-214-3p inhibits epithelial-to-mesenchymal transition and metastasis of endometrial cancer cells by targeting TWIST1
Abstract
Yuan-Yuan Fang,1,* Ming-Rong Tan,2,* Jian Zhou,1 Li Liang,1 Xiao-Yun Liu,3 Kun Zhao,4 Er-Chen Bao5 1Department of Gynaecology, Xu Zhou Maternal and Child Health Care Hospital, Xuzhou 221009, China; 2Department of Operation Room, Xiangyang No 1 People’s Hospital, Hubei University of Medicine, Xiangyang 441000, China; 3Central Laboratory, The Affiliated Hospital of Xu Zhou Medical University, Xuzhou 221009, China; 4Department of Laboratory, Xu Zhou Maternal and Child Health Care Hospital, Xuzhou 221009, China; 5Department of Gynaecology, Xinyi People’s Hospital, Xinyi 221400, China*These authors contributed equally to this workCorrespondence: Yuan-Yuan FangDepartment of Gynaecology, Xu Zhou Maternal and Child Health Care Hospital, No 46, Heping Road, Xuzhou 221009, Jiangsu, ChinaTel +86 139 5218 6059Email [email protected]: Substantive studies have described the ectopic microRNAs as a determinant of the pathogenesis of endometrial cancer (EC). miR-214-3p has been reported to be significantly downregulated in EC tissues, and its overexpression has been shown to inhibit the proliferation, migration, and invasion of EC cells. Our study sought to explore the molecular mechanism underlying the inhibitory effect of miR-214-3p on metastasis of EC cells.Methods: The expressions of miR-214-3p and TWIST1 in EC tissues and cells were detected by quantitative real-time PCR. Cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) were measured by transwell and Western blot analyses, respectively. The interaction between miR-214-3p and TWIST1 was confirmed by luciferase reporter assay. Xenograft tumor assay was performed to verify the role and underlying mechanism of miR-214-3p in EC in vivo.Results: miR-214-3p was downregulated and TWIST1 was upregulated in EC tissues and cells. miR-214-3p was negatively correlated with TWIST1 expression in EC tissues. Overexpression of miR-214-3p suppressed migration, invasion, and EMT in EC cells. TWIST1 was identified as a target of miR-214-3p in EC cells, and its overexpression significantly restored the inhibitory effects of miR-214-3p on cell migration, invasion, and EMT while its knockdown remarkably abolished miR-214-3p inhibitor-mediated promotion of progression of EC cells. Additionally, addition of miR-214-3p inhibited tumor growth by regulating EMT in vivo.Conclusion: miR-214-3p suppressed the EMT and metastasis of EC cells by targeting TWIST1, providing a novel biomarker for treatment of EC.Keywords: miR-214-3p, TWIST1, EMT, metastasis, endometrial cancer
