Circular RNA circ_0058123 Targets the miR-939-5p/RAC1 Pathway to Promote the Development of Colorectal Cancer

Abstract

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.

Keywords: Circ_0058123; Colorectal cancer; RAC1; miR-939-5p.