Circ_0000419 acts as a miR-580 sponge to accelerate colorectal cancer progression via regulating DNMT3B

Abstract

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to function in tumorigenesis and cancer progression. Nonetheless, the molecular mechanisms of circRNAs in colorectal cancer (CRC) have not been fully clarified.METHODS: The circRNA expression profile dataset GSE138589 was analyzed to find the differentially expressed circRNA in CRC. Circ_0000419, microRNA (miR)-580, and DNA methyltransferase 3 beta (DNMT3B) expressions in CRC were detected by qRT-PCR. The biological function of circ_0000419 on the growth, migration and invasion of CRC cells were analyzed by the CCK-8 method and Transwell experiment. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down experiment were performed to validate the interrelationship among circ_0000419, miR-580, and DNMT3B. Then the regulatory function of circ_0000419 and miR-580 on DNMT3B expression was then measured by Western blot.RESULTS: Circ_0000419 expression was up-regulated, and miR-580 expression was down-regulated in CRC tissues and cell lines. Circ_0000419 was positively linked to CRC patients’ T stage and lymph node metastasis. Circ_0000419 knockdown or miR-580 overexpression impeded CRC cells’ growth, migration, and invasion. Circ_0000419 expression was negatively correlated with miR-580 expression in CRC tissues. Circ_0000419 was identified as a molecular sponge for miR-580, and DNMT3B was identified as a targetgene of miR-580. Furthermore, miR-580 inhibition or DNMT3B overexpression reversed the biological effects of circ_0000419 knockdown on CRC cells’ proliferation, migration, and invasion.CONCLUSION: Circ_0000419 exerts a pro-cancer effect in modulating CRC cell proliferation, migration, and invasion by regulating the miR-580/DNMT3B axis.