MiR?501?3p promotes colorectal cancer progression via activation of Wnt/??catenin signaling.

ABSTRACT: Aberrant activation of Wnt/??catenin signaling is observed in >90% of colorectal cancer cases. microRNAs (miRNAs) regulate the expression of key genes in Wnt/??catenin signaling. As a result, abnormal expression of miRNAs regulates the activation of Wnt/??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/??catenin signaling, was a potential target gene of miR?501?3p. Inhibition of miR?501?3p increased APC expression in colorectal cancer cells. Additionally, ??catenin was destabilized following miR?501?3p inhibition; immunofluorescence analysis revealed that ??catenin translocated from nucleus to cytoplasm. In addition, cyclin D1 and c?Myc, two well?characterized target genes of Wnt/??catenin signaling, were downregulated following miR?501?3p inhibition. Transfection of APC small interfering RNA re?activated ??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 identified miR?501?3p as a novel regulator of Wnt/??catenin signaling in colorectal cancer cells via targeting APC, suggesting that miR?501?3p may act as a novel oncogenic miRNA in colorectal cancer.

SUBMITTER: Wu F 

PROVIDER: S-EPMC6685591 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature