Department of Gastrointestinal Surgery, the First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, China.
Department of Gastrointestinal Surgery, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, 353023, China.
Biochem Genet. 2024 Jun;62(3):1485-1501. doi: 10.1007/s10528-023-10485-8. Epub 2023 Aug 29.
Circular RNA (circRNA) can be used as a potential target for cancer treatment. However, the biological function and potential molecular mechanism of circ_0058123 in the development of colorectal cancer (CRC) are still unclear. The expression levels of circ_0058123, microRNA-939-5p (miR-939-5p) and Rac family small GTPase 1 (RAC1) were measured by quantitative real-time polymerase chain reaction or western blot assay. 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay, transwell assay, tube formation assay and flow cytometry apoptosis assay were conducted to assess CRC cell functions. In addition, protein expression was measured with western blot assay. Dual-luciferase reporter assays and RNA immunoprecipitation assay were conducted to confirm the relationships between miR-939-5p and circ_0058123, and miR-939-5p and RAC1. In vivo CRC tumor growth experiment also were carried out to determine circ_0058123-mediatede effects on tumor formation. Our data showed that circ_0058123 and RAC1 expression were increased, but miR-939-5p was decreased in both of CRC tissues and cell lines. Circ_0058123 depletion repressed CRC cell proliferation, migration, invasion and tube formation but promoted cell apoptosis. Down-regulation of circ_0058123 could significantly suppress the CRC progression, while the addition of miR-939-5p inhibitor could reverse this effect. Circ_0058123 directly targeted miR-939-5p, and RAC1 was a target of miR-939-5p. Furthermore, RAC1 overexpression could rescue the effect of miR-939-5p on CRC development. Lastly, silence of circ_0058123 inhibited CRC tumor growth in vivo. In conclusion, circ_0058123 could promote CRC progression through regulating the miR-939-5p/RAC1 axis and may be a valuable biomarker for early diagnosis and prognosis of CRC.
环状 RNA（circRNA）可以作为癌症治疗的潜在靶点。然而，circ_0058123 在结直肠癌（CRC）发展中的生物学功能和潜在分子机制仍不清楚。通过实时定量聚合酶链反应或 Western blot 检测 circ_0058123、microRNA-939-5p（miR-939-5p）和 Rac 家族小 GTP 酶 1（RAC1）的表达水平。采用 5-乙炔基-2'-脱氧尿苷（EdU）掺入实验、Transwell 实验、管形成实验和流式细胞术凋亡实验评估 CRC 细胞功能。此外，通过 Western blot 检测蛋白表达。通过双荧光素酶报告实验和 RNA 免疫沉淀实验验证 miR-939-5p 与 circ_0058123 以及 miR-939-5p 与 RAC1 之间的关系。还进行了体内 CRC 肿瘤生长实验以确定 circ_0058123 对肿瘤形成的介导作用。我们的数据表明，CRC 组织和细胞系中 circ_0058123 和 RAC1 的表达增加，而 miR-939-5p 的表达降低。circ_0058123 耗竭抑制 CRC 细胞增殖、迁移、侵袭和管形成，但促进细胞凋亡。下调 circ_0058123 可显著抑制 CRC 进展，而添加 miR-939-5p 抑制剂可逆转这种作用。circ_0058123 直接靶向 miR-939-5p，RAC1 是 miR-939-5p 的靶标。此外，RAC1 的过表达可以挽救 miR-939-5p 对 CRC 发育的影响。最后，沉默 circ_0058123 抑制体内 CRC 肿瘤生长。总之，circ_0058123 通过调节 miR-939-5p/RAC1 轴促进 CRC 进展，可能是 CRC 早期诊断和预后的有价值的生物标志物。
