Tumor recurrence and metastasis after surgical resection are the major causes for the cancer-related death of hepatocellular carcinoma (HCC). Thus, better understanding the mechanisms involved in tumor progression will benefit to improve HCC treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) play critical roles in the development and progression of HCC. However, the function of miR-519c-3p in HCC and its related mechanism remain unexplored. Here, we reported that miR-519c-3p was strongly overexpressed in HCC tissues, which was significantly correlated with poor prognosis and clinicopathological features including tumor size ≥5 cm, vascular invasion and advanced tumor-node-metastasis (TNM) stages (III + IV). Furthermore, the elevated levels of miR-519c-3p were observed in HCC cell lines. Subsequently, gain- or loss-of-function assays demonstrated that miR-519c-3p promoted HCC cell proliferation, migration as well as invasion in vitro, and facilitated the growth and metastasis of HCC cells in vivo. Mechanistically, B-cell translocation gene 3 (BTG3) was identified as a direct downstream target of miR-519c-3p. The level of BTG3 mRNA was downregulated in HCC and negatively correlated with miR-519c-3p expression. Western blotting confirmed that BTG3 was negatively regulated by miR-519c-3p in HCC cells. Luciferase reporter assays illustrated the direct interaction between miR-519c-3p and the 3'UTR of BTG3 mRNA. Recuse experiments demonstrated that BTG3 mediated the promoting effects of miR-519c-3p on the proliferation and motility of HCC cells. Collectively, our results suggest that miR-519c-3p functions as a tumor promotor in regulating the growth and metastasis of HCC by targeting BTG3, and potentially serves as a novel therapeutic target for HCC.
Keywords: BTG3; HCC; Tumor growth; Tumor metastasis; miR-519c-3p.
Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.