MicroRNA-376c-3p facilitates human hepatocellular carcinoma progression via repressing AT-Rich interaction domain 2

Abstract

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.