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.