Circ_0011232 contributes to hepatocellular carcinoma progression through miR-503-5p/AKT3 axis.

Abstract

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with high mortality. Circular RNAs (circRNAs) have been confirmed to be involved in the development of HCC, but the functions of circ_0011232 in HCC remain ill-defined. Quantitative real-time polymerase chain reaction, western blot assay, or immunohistochemistry assay was performed to determine the levels of circ_0011232, miR-503-5p, and AKT3. RNase R assay and actinomycin D assay were conducted to analyze the feature of circ_0011232. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, flow cytometry analysis, wound-healing assay, and transwell assay were conducted to evaluate HCC cell proliferation, colony formation, apoptosis, migration, and invasion. Dual-luciferase reporter assay was carried out to confirm the relationships among circ_0011232, miR-503-5p, and AKT3. The murine xenograft assay was conducted to verify the function of circ_0011232 in tumor growth in vivo. Circ_0011232 and AKT3 were upregulated, while miR-503-5p was decreased in HCC tissues and cells. Circ_0011232 knockdown repressed HCC cell proliferation, colony formation, migration, and invasion, and promoted apoptosis in vitro and blocked tumor growth in vivo. MiR-503-5p was a target of circ_0011232. MiR-503-5p inhibition reversed the effects of circ_0011232 knockdown on HCC cell development. Moreover, AKT3 was confirmed to be a target of miR-503-5p, and AKT3 overexpression abolished the inhibitory effects on HCC cell progression caused by miR-503-5p. Circ_0011232 facilitated HCC progression via miR-503-5p/AKT3 axis, which might provide a novel treatment strategy for HCC.