Circ_0037866 Contributes to the Tumorigenesis of Renal Cell Carcinoma by Sequestering miR-384 to Elevate Chromobox 5 Expression

Abstract

<b><i>Background:</i></b> Circular RNAs (circRNAs) were demonstrated to have roles in the carcinogenesis of renal cell carcinoma (RCC). Hence, this work aimed to determine the functions and molecular mechanism of circ_0037866 in regulating the progression of RCC. <b><i>Methods:</i></b> Quantitative real-time polymerase chain reaction and Western blotting were used to detect the levels of genes and proteins. In vitro assays, including colony formation, 5-ethynyl-2′-deoxyuridine, flow cytometry, transwell assays, and in vivo tumor formation, were conducted to investigate the effects of circ_0037866 on RCC tumorigenesis. Dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the interaction between miR-384 and circ_0037866 or Chromobox 5 (CBX5). <b><i>Results:</i></b> Circ_0037866 is a stable circRNA and was found to be increased in RCC tissues and cells. Functionally, circ_0037866 silencing suppressed RCC cell survival, invasion, and migration in vitro, and impeded RCC cell tumorigenesis in the subcutaneous xenograft model. Mechanistically, circ_0037866 could function as a sponge for miR-384 to elevate the expression of its target CBX5. Furthermore, a series of rescue experiments showed that miR-384 inhibition reversed the anticancer effects of circ_0037866 knockdown on RCC cells; besides that, miR-384 restoration suppressed RCC cell growth and mobility, which were attenuated by CBX5 overexpression. <b><i>Conclusion:</i></b> Circ_0037866 knockdown restrains the tumorigenesis of RCC by miR-384/CBX5, revealing a promising molecular target for RCC therapy.