The correlation between microRNA490-3p and TGFα in endometrial carcinoma tumorigenesis and progression
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Kai-Xuan Sun1, Ying Chen2, Shuo Chen1, Bo-Liang Liu1, Miao-Xiao Feng1, Zhi-Hong Zong3 and Yang Zhao1
1 Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China
2 Department of Gynecology, The Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
3 Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, P.R. China
Yang Zhao, email:
Keywords: endometrial carcinoma, microRNA, TGFα, carcinogenesis, metastasis
Received: November 17, 2015 Accepted: January 18, 2016 Published: January 28, 2016
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3’-untranslated region (3’ UTR). MiR-490-3p has been reported to be a suppressor in various human cancers; however, little is known about the biological functions of miR-490-3p in endometrial cancer (EC). In our study, we found that MiR-490-3p mRNA expression was significantly lower in ECs than in normal endometrial tissues. MiR-490-3p mRNA expression was also negatively associated with depth of invasion (mucosa vs. muscular and serosa) and lymph node metastasis (negative vs. positive) in EC. MiR-490-3p overexpression reduced proliferation; promoted G1 arrest and apoptosis; suppressed migration and invasion; and reduced TGFα, NF-kB, cyclin D1, survivin, matrix metalloproteinase 2 (MMP2) mRNA and protein expression, and improved Bax mRNA and protein expression. The dual-luciferase reporter assay indicated that miR-490-3p directly targeted TGFα by binding its 3’ untranslated region. MiR-490-3P transfection also suppressed tumor development and TGFα expression (as determined by immunohistochemistry and western blotting) in vivo in the xenograft mouse model. This is the first demonstration that miR-490-3P might act as a suppressor in EC tumorigenesis and progression by targeting TGFα. Our results provide a theoretical basis for the further study on the molecular target for endometrial cancer.
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