Circ_0084615 is an oncogenic circular RNA in colorectal cancer and promotes DNMT3A expression via repressing miR-599

Abstract

BackgroundCircular RNAs (circRNAs) are implicated in modulating cancer progression, exerting a pro- or anti-cancer effect. This work is aimed to probe the biological function of circ_0084615 in colorectal cancer (CRC) and its underlying mechanism. MethodsCirc_0084615 was selected from two circRNA microarray datasets (GSE138589 and GSE142837). Circ_0084615, microRNA (miR)-599 and DNA methyltransferases 3A (DNMT3A) mRNA expression in CRC tissues and cell lines were examined by qRT-PCR. The relationship between circ_0084615 expression level and clinical features were analyzed with chi-square test. Circ_0084615 knockdown model was constructed by siRNA in two CRC cell lines. The biological functions of circ_0084615 in CRC cells were evaluated by CCK-8 and Transwell experiments. The effect of circ_0084615 on CRC cell metastasis in vivo was examined with lung metastasis model of nude mice. Dual luciferase reporter gene assay was used to determine whether circ_0084615 and miR-599, and miR-599 and DNMT3A interacted with each other. Western blot was employed to examine the regulatory effects of circ_0084615 and miR-599 on DNMT3A protein expression in CRC cells. ResultsCirc_0084615 was up-regulated in CRC and was correlated with poor overall survival rate and advanced clinical stage of CRC patients. Functional assays validated that depletion of circ_0084615 impeded CRC cell proliferation, migration and invasion. Circ_0084615 acted as a molecular sponge for miR-599 to repress its expression. DNMT3A was a downstream target of miR-599. Functional compensation experiments showed that miR-599 inhibitors partially counteracted the the biological effects of silencing circ_0084615 on CRC cells. ConclusionsCirc_0084615 is a tumor-promoting circRNA in CRC that functions as a competing endogenous RNA to regulate DNMT3A expression via sponging miR-599. Our research provides a potential therapeutic target for CRC patients.