Abstract
The aim of the present research is to explore the biological function and mechanism of circ_0082319 in HCC progression. Circ_0082319, microRNA-505-3p (miR-505-3p), protein tyrosine kinase 2 (PTK2), and human antigen R (HuR, also known as ELAVL1) level were detected by real-time quantitative polymerase chain reaction. Cell viability, proliferation, apoptosis, invasion, and angiogenesis were measured using (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels of c-Myc, MMP2, PTK2, and HuR were examined using western blot. The glycolysis levels were assessed using specific kits. Binding between miR-505-3p and circ_0082319 or PTK2 was predicted by Starbase and verified by a dual-luciferase reporter and RNA immunoprecipitation assays. The biological role of circ_0082319 on HCC tumor growth was examined using xenograft tumor model in vivo. Circ_0082319, PTK2, and HuR were highly expressed, and miR-505-3p was reduced in HCC samples and cell lines. Moreover, the knockdown of circ_0082319 might repress HCC cell proliferation, invasion, angiogenesis, and induce apoptosis in vitro. In mechanism, circ_0082319 served as a sponge of miR-505-3p to regulate PTK2 expression. HuR expedited circ_0082319 expression in HCC cells. HuR-mediated circ_0082319 might accelerate HCC cell proliferation, invasion, angiogenesis, and suppress apoptosis by the miR-505-3p/PTK2 axis, hinting at a promising therapeutic target for HCC treatment.
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The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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This research was supported by the special fund of Basic Scientific Research Operation Expenses of Universities in Henan Province (No. NSFRF230423).
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C.Q. and S.L. designed and supervised the study, conducted the experiments, and drafted the manuscript. W.C. and D.X. collected and analyzed the data. T.G. and B.W. operated the software and edited the manuscript. All authors reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Qin, C., Liu, S., Chen, W. et al. HuR-induced circ_0082319 contributes to hepatocellular carcinoma by elevating PTK2 through miR-505-3p. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3111–3126 (2024). https://doi.org/10.1007/s00210-023-02793-y
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DOI: https://doi.org/10.1007/s00210-023-02793-y