miR-99b-3p promotes hepatocellular carcinoma metastasis and proliferation by targeting protocadherin 19

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, with characteristics of high morbidity and mortality. Identifying clinically practical targets and uncovering the potential mechanism for HCC were urgent for us. Though aberrantly expressed miR-99b-3p has been reported in several cancers, the expression and roles of miR-99b-3p in HCC remain uncovered. In the present study, we demonstrated for the first time that miR-99b-3p was overexpressed in HCC by our findings and data from GEO datasets. Statistical analysis revealed that highly expressed miR-99b-3p was closely related to malignant clinicopathological characteristics and poorer prognosis of HCC patients. Furthermore, results from Wound healing assay, Transwell assays, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay and 5-ethynyl-2'-deoxyuridine (EdU) assay revealed that miR-99b-3p played a promoting role in migration, invasion and proliferation of HCC cells. Then, by bioinformatics tools, luciferase reporter gene assay, integrative database analysis, and Pearson correlation analysis and so on, protocadherin 19 (PCDH19) was identified as the target of miR-99b-3p in HCC cells. Furthermore, rescue experiments were conducted to confirm the mediator role of PCDH19 for miR-99b-3p. Collectively, we demonstrate that miR-99b-3p promotes HCC metastasis and proliferation by directly targeting PCDH19. MiR-99b-3p may become a potential therapy target for HCC.

Keywords: Hepatocellular carcinoma; Metastasis; PCDH19; Proliferation; miR-99b-3p.