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

Abstract

Background: 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. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to detect the levels of genes and proteins. In vitro assays, including colony formation, 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, transwell assays, and in vivo tumor formation were conducted to investigate the effects of circ_0037866 on RCC tumorignesis. Dual-luciferase reporter assay, RNA-pull down and RIP assay were used to confirm the interaction between miR-384 and circ_0037866 or CBX5 (Chromobox 5). Results: Circ_0037866 is 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. Conclusion: Circ_0037866 knockdown restrains the tumorigenesis of RCC by miR-384/CBX5, revealing a promising molecular target for RCC therapy.

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

“…Overexpression of CBX5 or inhibition of miR-589-5p in renal cell carcinoma (RCC) reverses the inhibitory effect of silencing lysyl oxidase like 1-AS1 on the proliferation and migration of RCC cells (176). Circ_0037866 may sponge miR-384 to increase the expression of its target, CBX5, thereby promoting the survival, invasion and migration of RCC cells in vitro and in vivo (177).…”