miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma

• Published in: Frontiers in bioscience Vol. 25; no. 6; pp. 1120 - 1131
• Main Author: Xu, Chunquan
• Format: Journal Article
• Language: English
• Published: Singapore IMR Press 01.03.2020
• Subjects: 3' Untranslated Regions - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Down-Regulation; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; hcc; Hep G2 Cells; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; MicroRNAs - genetics; mir-4698; motility; RNA Interference; trim59; Tripartite Motif Proteins - genetics; Tripartite Motif Proteins - metabolism
• DOI: 10.2741/4849
• ISSN: 1093-9946; 2768-6701

microRNAs (miRNAs) are important players in tumor suppression and oncogenesis. In this study, we aimed to explore the role of miR-4698 with its potential target tripartite motif-containing 59 (Trim59), a protein with oncogenic function, in hepatocellular carcinoma (HCC). The expression of miR-4698 was significantly lower in HCC tissues and HCC cell lines compared to normal tissues adjacent to tumors and in normal hepatic cell lines. Overexpression of miR-4698 in HCC cells by transfection of its mimic significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas its antisense oligonucleotides (ASOs) exerted the opposite effect. Trim59 was identified as a target of miR-4698 in miRDB, and consistent with this prediction, the expression of Trim59 was inversely correlated with that of miR-4698 in HCC, and miR-4698 overexpression led to a significant decrease in the luciferase activity of pRL-Trim59-3'-UTR but not mutant pRL-Trim59-3'-UTR. Moreover, the miR-4698 mimic inhibited the expression of Trim59. Overexpression of Trim59 abrogated the inhibitory effects of miR-4698. In conclusion, these data show that the miR-4698-Trim59 axis plays a tumor-suppressive role in HCC.