J Cancer 2019; 10(15):3407-3419. doi:10.7150/jca.30858

Research Paper

MiR-HCC2 Up-regulates BAMBI and ELMO1 Expression to Facilitate the Proliferation and EMT of Hepatocellular Carcinoma Cells

Jianying Yi1*, Yajie Fan1*, Le Zhang1*, Hong Wang1, Ting Mu1, Hong Xie1, Huijie Gao1, Min Liu1, Shengping Li2, Hua Tang1✉

1. Tianjin Life Science Research Center and Department of Pathogen Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
2. State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, 651 Dong-Feng Road East, Guangzhou 510060, China
*These authors contributed equally to this work

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Citation:
Yi J, Fan Y, Zhang L, Wang H, Mu T, Xie H, Gao H, Liu M, Li S, Tang H. MiR-HCC2 Up-regulates BAMBI and ELMO1 Expression to Facilitate the Proliferation and EMT of Hepatocellular Carcinoma Cells. J Cancer 2019; 10(15):3407-3419. doi:10.7150/jca.30858. Available from http://www.jcancer.org/v10p3407.htm

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Abstract

MicroRNAs (miRNAs) are a class of gene expression regulators that participate in the occurrence and development of hepatocellular carcinoma (HCC), although the underlying mechanism by which they function in HCC has not been fully elucidated. Here, small RNA deep sequencing was used to identify aberrantly expressed miRNAs in HCC tissues, and a novel miRNA named miR-HCC2 was identified. RT-qPCR analysis demonstrated that miR-HCC2 displayed higher expression in HCC tissues than in adjacent non-tumor tissues. We documented that miR-HCC2 facilitated the growth, migration and invasion of HCC cells by accelerating cell cycle progression, incressing the expression of epithelial-to-mesenchymal transition (EMT)-associated marker vimentin but decreasing the expression of E-cadherin. MiR-HCC2 directly targeted the 3′ UTR of BAMBI and ELMO1 and up-regulated their expression. Both BAMBI and ELMO1 had the same patterns of expression with miR-HCC2 in HCC tissues. Additionally, blocking BAMBI or ELMO1 counteracted the phenotypic alterations elicited by miR-HCC2. Collectively, our investigation identified miR-HCC2 as a new positive modulator of HCC aggressiveness that may serve as a potential biomarker for the development of diagnostic and therapeutic approaches for HCC.

Keywords: BAMBI, ELMO1, HCC, miRNAs, migration, invasion