miR-501-3p promotes colorectal cancer progression via activation of Wnt/ß-catenin signaling

Abstract

Aberrant activation of Wnt/β-catenin signaling is observed in >90% of colorectal cancer cases. microRNAs (miRNAs) regulate the expression of key genes in Wnt/β-catenin signaling. As a result, abnormal expression of miRNAs regulates the activation of Wnt/β-catenin signaling in several types of cancer. In the current study, it was demonstrated that miR-501-3p was overexpressed in colorectal tumor tissues compared to the adjacent normal tissues. Downregulation of miR-501-3p inhibited cell proliferation and sphere formation, while it induced cell cycle arrest at the G1 phase in colorectal cancer cells. Bioinformatics analysis results predicted that adenomatous polyposis coli (APC), a negative regulator of Wnt/β-catenin signaling, was a potential target gene of miR-501-3p. Inhibition of miR-501-3p increased APC expression in colorectal cancer cells. Additionally, β-catenin was destabilized following miR-501-3p inhibition; immunofuorescence analysis revealed that β-catenin translocated from nucleus to cytoplasm. In addition, cyclin D1 and c-Myc, two well-characterized target genes of Wnt/β-catenin signaling, were downregulated following miR-501-3p inhibition. Transfection of APC small interfering RNA re-activated β-catenin and stimulated the expression of cyclin D1 and c-Myc. Furthermore, silencing of APC reversed the miR-501-3p inhibitor-induced cell cycle disruption, and the inhibition of cell proliferation and sphere formation in colorectal cancer cells. In conclusion, the present study identifed miR-501-3p as a novel regulator of Wnt/β-catenin signaling in colorectal cancer cells via targeting APC, suggesting that miR-501-3p may act as a novel oncogenic miRNA in colorectal cancer.