Abstract

BACKGROUND: This study aimed to investigate the expression of microRNA-639 (miR-639) in tumor tissue from patients with hepatocellular carcinoma (HCC) and its effects on patient outcome, to identify the targets for miR-639 using bioinformatics and luciferase reporter analysis, and the effects of miR-639 in human HCC cells in vitro to identify the molecular pathways involved.

MATERIAL AND METHODS: Expression levels of miR-639 were compared in tumor tissue and adjacent normal liver tissue from 50 patients with HCC, and Kaplan-Meier curves identified the association with overall survival (OS). miR-639 expression was measured in HCC cells cultured in vitro using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot. HCC cells were studied using the MTT assay, the colony formation assay, and the transwell assay. Bioinformatics and luciferase reporter analysis identified the role of the histone acetyltransferase gene, KAT7, in HCC.

RESULTS: The expression of miR-639 was significantly reduced in HCC tissues compared with normal adjacent liver tissues, and inhibited cell proliferation and epithelial-mesenchymal transition (EMT) of HCC cells. Bioinformatics and luciferase reporter analysis showed that miR-639 directly targeted KAT7 and inhibit its expression. KAT7 expression promoted cell proliferation, and migration of human HCC cells in vitro, and miR-639 inhibited cell proliferation and EMT by down-regulating the KAT7/Wnt/β-catenin signaling pathway.

CONCLUSIONS: miR-639 was down-regulated in HCC tumor tissue, and inhibited proliferation and migration of HCC cells by the down-regulation of KAT7/Wnt/β-catenin signaling and was associated with reduced OS. These findings supported the potential role of miR-639 as a tumor suppressor.

Keywords: Carcinoma, Hepatocellular, Epithelial-mesenchymal transition, Wnt Signaling Pathway, Base Sequence, Down-Regulation, Gene Expression Regulation, Neoplastic, Histone Acetyltransferases, Liver Neoplasms, Middle Aged, Survival Analysis