Circ_0085315 promotes cell proliferation, invasion, and migration in colon cancer through miR-1200/MAP3K1 signaling pathway

Abstract

ABSTRACT Colon cancer (CC) is a common malignant tumor of the digestive tract. Circular RNAs (circRNAs) play important roles in the progression of CC. This study aimed to explore the role and mechanism of circRNA_0085315 in CC. In this study, we used qRT-PCR and Western blot assays to analyze the expressions of circRNA, miRNA, and mRNA as well as the expression of the related proteins. Luciferase reporter, RNA pull-down, and qRT-PCR assays were used to prove the relationship among circRNA, miRNA, and mRNA. CCK-8, colony formation, and transwell assays were used to perform the analysis of cell proliferation, migration, and invasion. Our results showed that the higher circRNA_0085315 expression led to the poorer prognosis of CC patients. The function of circRNA_0085315 as a ceRNA in competing with MAP3K1 mRNA to sponge miR-1200. CircRNA_0085315 sponged miR-1200 to promote cell proliferation, migration, and invasion and affected the expression of Ki67, MMP2, E-cadherin, and N-cadherin, but not circRNA_0085315-mut without the binding site of miR-1200. MAP3K1-overexpression or miR-1200 mimics prevented the suppression on the enhanced cell proliferation, migration, and invasion caused by circRNA_0085315-overexpression. circRNA_0085315 increased the phosphorylation levels of JNK, p38, and ERK1/2 by stimulating MAP3K1 up-regulation caused by miR-1200 inhibition. In conclusion, circRNA_0085315 serves as a ceRNA and promotes CC progression through the activation of the MAPK signaling pathway mediated via the miR-1200/MAP3K1 axis, suggesting that circRNA_0085315 may be a promising diagnostic and therapeutic target for CC.