Circ_0046600 promotes hepatocellular carcinoma progression via up-regulating SERBP1 through sequestering miR-1258

Abstract

BackgroundCirc_0046600 was reported to promote hepatocellular carcinoma (HCC) cell migratory ability. However, the functional roles and mechanism of circ_0046600 in HCC remain largely unknown. MethodsLevels of genes and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro experiments were performed using cell counting kit-8 (CCK-8), colony formation, transwell, flow cytometry and Western blot assays, respectively. The direct interactions between miR-1258 and circ_0046600 or SERPINE1 mRNA-binding protein 1 (SERBP1) was verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft tumor model was established to perform in vivo assay. Exosomes were obtained from culture media by using the commercial kit. ResultsCirc_0046600 was highly expressed in HCC tissues and cells. Silencing of circ_0046600 impaired HCC cell growth and metastasis in vitro, as well as impeded HCC tumor growth in vivo. Mechanistically, circ_0046600 could competitively target miR-1258 to prevent the degradation of its target gene SERBP1. Rescue assay showed that miR-1258 inhibition reversed the inhibitory effects of circ_0046600 silencing on HCC cell. Moreover, ectopic overexpression of miR-1258 suppressed cell growth and metastasis in HCC, which was abolished by SERBP1 up-regulation. Furthermore, circ_0046600 was packaged into exosomes and could be derived from HCC cells. ConclusionCirc_0046600 promoted HCC progression via up-regulating SERBP1 through sequestering miR-1258; besides that, circ_0046600 was packaged into exosomes and could be released from HCC cells.