microRNA-19a-3p and microRNA-376c-3p Promote Hepatocellular Carcinoma Progression Through SOX6-Mediated Wnt/β-Catenin Signaling Pathway

BACKGROUND: Recent researches have suggested that microRNA (miR)-19a-3p and miR-376c-3p might function as initiators in diverse cancers. Based on which, in this current study, we aimed to probe into the combined effects and mechanisms of miR-19a-3p and miR-376c-3p in hepatocellular carcinoma (HCC) cells. METHODS: Tumor tissues and adjacent normal tissues from 21 cases of HCC patients, HCC cell lines, and human normal liver cell lines were used in this study. RT-qPCR and Western blot were implemented to detect the expression of miR-19a-3p, miR-376c-3p, SOX6, and Wnt/β-catenin pathway-associated factors in HCC tissues and cells. The direct relationships between miR-19a-3p or miR-376c-3p and SOX6 were confirmed by luciferase activity assay. HCC cells were treated with miR-19a-3p inhibitor, miR-376c-3p inhibitor, or oe-SOX-6 to figure out their functions in HCC malignancy. The in vivo assays were conducted for the confirmation of in vitro results. RESULTS: In both HCC tissues and cells, miR-19a-3p and miR-376c-3p were highly expressed, and SOX6 was poorly expressed. Depleted miR-19a-3p or miR-376c-3p was found to result in retarded HCC development. Bioinformatics analysis and luciferase activity assay revealed that SOX6 was the common target gene of miR-19a-3p and miR-376c-3p. Overexpressed SOX6 was demonstrated to block the Wnt/β-catenin pathway, thereby slowing down HCC progression. The in vivo assays showed that suppressed miR-19a-3p or miR-376c-3p and elevated SOX6 could reduce the tumor volume and weight of nude mice. CONCLUSION: This study suggests that miR-19a-3p/miR-376c-3p activates the Wnt/β-catenin pathway via targeting SOX6, contributing to promoted biological functions of HCC cells.