Department of Interventional, The First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Democratic South Road 17, Jiefang District, Jiaozuo, 454000, China.
Department of Endocrinology, The First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, 454000, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):3111-3126. doi: 10.1007/s00210-023-02793-y. Epub 2023 Oct 25.
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.
本研究旨在探索 circ_0082319 在 HCC 进展中的生物学功能和机制。通过实时定量聚合酶链反应检测 circ_0082319、微小 RNA-505-3p（miR-505-3p）、蛋白酪氨酸激酶 2（PTK2）和人抗原 R（HuR，也称为 ELAVL1）的水平。采用（4-5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐（MTT）测定细胞活力、增殖、凋亡、侵袭和血管生成，5-乙炔基-2'-脱氧尿苷（EdU）、流式细胞术、transwell 和管形成测定法。使用 Western blot 检测 c-Myc、MMP2、PTK2 和 HuR 的蛋白水平。通过特定试剂盒评估糖酵解水平。Starbase 预测 miR-505-3p 与 circ_0082319 或 PTK2 之间的结合，并通过双荧光素酶报告和 RNA 免疫沉淀测定验证。体内异种移植肿瘤模型研究 circ_0082319 对 HCC 肿瘤生长的生物学作用。HCC 样本和细胞系中 circ_0082319 表达升高，PTK2 和 HuR 表达降低，miR-505-3p 表达降低。此外，circ_0082319 的敲低可能会抑制 HCC 细胞的增殖、侵袭、血管生成，并在体外诱导细胞凋亡。在机制上，circ_0082319 作为 miR-505-3p 的海绵体调节 PTK2 的表达。HuR 加速 HCC 细胞中 circ_0082319 的表达。HuR 介导的 circ_0082319 可能通过 miR-505-3p/PTK2 轴加速 HCC 细胞的增殖、侵袭、血管生成，并抑制细胞凋亡，提示其可能成为 HCC 治疗的有前途的治疗靶点。
