Paclitaxel (PTX) is an effective chemotherapeutic agent for cancer patients. It has been reported that circular RNA (circRNA) circ_0005785is involved in the progression of hepatocellular carcinoma (HCC). The purpose of this study is to explore the role and mechanism of circ_0005785 in the PTX resistance of HCC. Cell viability, proliferation, invasion, migration, apoptosis, and angiogenesis were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, transwell, wound-healing, flow cytometry, and tube formation assay. Circ_0005785, microRNA-640 (miR-640), and Glycogen synthase kinase-3 beta (GSK3β) levels were detected using real-time quantitative polymerase chain reaction. Protein levels of Proliferating cell nuclear antigen (PCNA), Bcl-2, and GSK3β were measured using western blot assay. After being predicted using Circular RNA interactome or TargetScan, binding between miR-640 and circ_0005785 or GSK3β was verified using dual-luciferase reporter and RNA Immunoprecipitation assay. PTX treatment could repress HCC cell viability, decrease circ_0005785 and GSK3β expression, and increase the miR-640 level in HCC cell lines. Furthermore, circ_0005785 and GSK3β were increased, and miR-640 was decreased in HCC tissues and cell lines. Moreover, circ_0005785 knockdown hindered proliferation, migration, invasion, angiogenesis, and boosted apoptosis in PTX-treated HCC cells in vitro. In addition, circ_0005785 silencing improved the PTX sensitivity of HCC in vivo. Mechanistically, circ_0005785 acted as a sponge of miR-640 to regulate GSK3β expression. PTX restrained HCC tumorigenesis partly via regulating the circ_0005785/miR-640/GSK3β axis, hinting at a promising therapeutic target for the HCC treatment.
Keywords: Circ_0005785; GSK3β; HCC; PTX; miR-640.
© 2023 International Federation for Cell Biology.