Circ_0000517 contributes to hepatocellular carcinoma progression by upregulating ARID4B via sponging miR-328-3p.

Abstract

BACKGROUND\nCircular RNAs (circRNAs) have been demonstrated as important regulators in tumor progression, including hepatocellular carcinoma (HCC). Therefore, the functional effects of circ_0000517 are investigated in HCC.\n\n\nMETHODS\nThe real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression levels of circ_0000517, microRNA-328-3p (miR-328-3p), and AT-rich interaction domain 4B (ARID4B) in HCC tissues and cells. The proliferation ability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony formation assays. Flow cytometry assay was performed to assess apoptosis and cell cycle distribution. Glycolysis was analyzed by extracellular acidification rate (ECAR) assay. The effects of circ_0000517 inhibition on tumor growth was assessed by a xenograft experiment. The interaction relationship between miR-328-3p and circ_0000517 or ARID4B was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. The protein expression level of ARID4B was quantified by western blot assay.\n\n\nRESULTS\nCirc_0000517 was significantly upregulated in HCC tissues and cells compared to controls; besides, cisplatin (DDP)-resistant tissues and cells showed higher expression of circ_0000517 compared with sensitive groups. The downregulation of circ_0000517 decreased proliferation and glycolysis while induced cell cycle arrest and apoptosis in DDP-resistant HCC cells, which was abolished by silencing of miR-328-3p. In vivo studies also suggested that suppression of circ_0000517 retarded the growth of xenograft tumors. MiR-328-3p was a target of circ_0000517, and it was negatively regulated by circ_0000517. Furthermore, the upregulation of ARID4B overturned miR-328-3p-induced inhibitory effects on HCC progression.\n\n\nCONCLUSION\nMechanistically, circ_0000517 stimulated pathological process of HCC by regulating miR-328-3p/ARID4B axis, suggesting a new insight into the diagnosis of HCC.