CircRNA circUGGT2 Contributes to Hepatocellular Carcinoma Development via Regulation of the miR-526b-5p/RAB1A Axis.

Abstract

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor in the world. Circular RNA hsa_circ_0008274 (circUGGT2) is reported to be upregulated in HCC tissues. Notwithstanding, the role and regulatory mechanism of circUGGT2 in HCC are indistinct.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was implemented to examine the levels of circUGGT2, microRNA (miR)-526b-5p, and ras-related protein Rab-1A (RAB1A) mRNA in HCC tissues and cells. Cell proliferation and colony formation were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) or colony formation assays. The levels of cyclin D1, proliferating cell nuclear antigen (PCNA), and RAB1A were detected with Western blotting. Cell cycle progression, migration, and invasion were evaluated by using flow cytometry or transwell assays. The relationship between circUGGT2 or RAB1A and miR-526b-5p was verified via dual-luciferase reporter and/or RNA pull-down assays. Xenograft assay was executed to confirm the role of circUGGT2 in vivo.ResultsWe observed that circUGGT2 and RAB1A were upregulated while miR-526b-5p was downregulated in HCC tissues and cells. CircUGGT2 silencing suppressed tumor growth in vivo and curbed proliferation, colony formation, cell cycle progression, migration, and invasion of HCC cells in vitro. Mechanically, circUGGT2 regulated RAB1A expression via competitively binding to miR-526b-5p. Also, the inhibitory influence of circUGGT2 silencing on the malignancy of HCC cells was overturned by miR-526b-5p inhibitor. Furthermore, RAB1A overexpression reversed the suppressive influence of miR-526b-5p mimic on the malignancy of HCC cells.ConclusionCircUGGT2 silencing inhibited HCC development via modulating the miR-526b-5p/RAB1A axis, providing a possible target for HCC treatment.