Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells.

BACKGROUND: Aberrant expression of microRNAs contributes to tumor growth and progression.

AIMS: This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC).

METHODS: The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330.

RESULTS: The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330.

CONCLUSIONS: Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.