Circular RNA circ_0021093 regulates miR-432/Annexin A2 pathway to promote hepatocellular carcinoma progression.

Abstract

Hepatocellular carcinoma (HCC) is a major histological subtype of liver cancer cases. Previous studies showed that circular RNA (circRNA) circ_0021093 was upregulated in HCC, but the regulatory mechanism of circ_0021093 is still rare. The expression levels of circ_0021093, miR-432 and Annexin A2 (ANXA2) were analyzed by real-time quantitative PCR. The relationship between the overall survival time of HCC patients and circ_0021093 level was analyzed with Kaplan-Meier analysis. Cell proliferation, migration and invasion were examined with cell counting kit-8 and transwell assays. Western blot was used to assess the protein expression of epithelial-mesenchymal transition markers and ANXA2. In addition, loss- or gain-of-function experiments and dual-luciferase reporter assay were performed to probe the relationship between miR-432 and circ_0021093 or ANXA2. The influences of circ_0021093 silencing in vivo were measured by using xenograft models. Circ_0021093 was highly expressed in HCC tissues and cells, and its level was associated with poor prognosis of HCC patients. Functional experiments showed that knockdown of circ_0021093 repressed proliferation, migration and invasion in vitro and tumor growth in vivo by regulating miR-432, while upregulation of circ_0021093 reversed these results. Moreover, miR-432 negatively regulated ANXA2 expression in HCC, and introduction of ANXA2 could abolish overexpression of miR-432-induced effects on HCC cells. Collectively, circ_0021093 boosted HCC progression via regulating proliferation, migration and invasion of HCC cells by acting as competing endogenous RNA to sponge miR-432.