J Cancer 2018; 9(22):4187-4196. doi:10.7150/jca.27939 This issue

Research Paper

MicroRNA-376c-3p Facilitates Human Hepatocellular Carcinoma Progression via Repressing AT-Rich Interaction Domain 2

Yuan Wang1, Weiping Chang2, Wanli Chang2, Xiaowei Chang2, Song Zhai1, Guoying Pan1, Shuangsuo Dang1✉

1. Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an 710004, China
2. Department of General Surgery, the First Affiliated Hospital of Xi'an Medical University, 48 Fenghao West Road, Xi'an 710077, China

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Wang Y, Chang W, Chang W, Chang X, Zhai S, Pan G, Dang S. MicroRNA-376c-3p Facilitates Human Hepatocellular Carcinoma Progression via Repressing AT-Rich Interaction Domain 2. J Cancer 2018; 9(22):4187-4196. doi:10.7150/jca.27939. Available from https://www.jcancer.org/v09p4187.htm

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Hepatocellular carcinoma (HCC), accounting for approximately 90% of liver cancer, is the most lethal malignant tumors in the world. Large amount of evidence indicate that microRNAs (miRNAs) contribute to the tumorigenesis and progression of HCC. Among them, miR-376c-3p was recently identified as a tumor-related miRNA and is up-regulated in HBV-related HCC. But, the clinical significance of miR-376c-3p and its biological function in HCC progression are still unclear. Here, we confirmed that miR-376c-3p expression level in HCC was markedly higher than that in noncancerous tissues. Up-regulation of miR-376c-3p was detected in four different HCC cell lines. High miR-376c-3p expression correlated with poor prognostic features, such as large tumor size and venous infiltration. Follow-up data indicated that high miR-376c-3p level evidently correlated with poor clinical outcomes of HCC patients. Moreover, knockdown of miR-376c-3p repressed HCC cell growth, migration and invasion in vitro. miR-376c-3p overexpression facilitated these malignant behaviors of Bel-7402 cells. Mechanistically, miR-376c-3p posttranscriptionally repressed ARID2 expression by directly interacting with its 3'-UTR. Furthermore, an obvious negative correlation between miR-376c-3p and ARID2 mRNA expression in HCC tissues was confirmed. Notably, miR-376c-3p knockdown suppressed HCC growth and metastasis in nude mice. Gain-of-function experiments showed that ARID2 inhibited cell growth and mobility of Hep3B cells. Subsequently, ARID2 knockdown rescued miR-376c-3p silencing attenuated Hep3B cell proliferation and mobility. Our results suggest that miR-376c-3p exerts an oncogenic role in HCC progression.

Keywords: miR-376c-3p, hepatocellular carcinoma, ARID2, proliferation, invasion