circIFT80 Functions as a ceRNA for miR-142, miR-568, and miR-634 and Promotes the Progression of Colorectal Cancer by Targeting β-Catenin

Abstract

Colorectal cancer (CRC) is the third most common form of malignant tumor and is characterized by high rates of proliferation and metastases. Circular RNAs (circRNAs) are a form of noncoding and closed loop RNA molecules and play vital roles in the progression of various types of cancer in humans. Here, we used circRNA microarray sequencing technology to analyze the different circRNAs between CRC tissues and normal tissues and explore the role of circIFT80 in progression of colorectal cancer. In this present study, we found that circIFT80 was abnormally overexpression in colorectal cancer tissues and tumor cells. While knockout circIFT80 in HT29 cell or SW480 cells, the proliferation, and migration of the cells were inhibited, the cell cycle was arrested in G2/M phase, and the cell apoptosis was increased. And then, we found circIFT80-positive correlation with CTNNB1 (β-catenin) by sponging miR-142, miR-568, and miR-634 upregulated the gene expression. These miRNAs which targeted β-catenin mRNA were confirmed by dual-luciferase reporter system and RNA-pulldown. In addition, xenograft tumor experiments showed that circIFT80 accelerated the tumorigenesis of CRC in vivo. In conclusion, our work reveals the impacts of circIFT80 as ceRNA in the progression of CRC, by which sponging miR-142, miR-568, and miR-634 enhanced the expression levels of β-catenin and activation Wnt/β-catenin pathway. Collectively, our data indicate that circIFT80 serves as an oncogene in CRC and represents a novel candidate for diagnosis and treatment.