[No authors listed]
Aberrant activation of Wnt/βâcatenin signaling is observed in >90% of colorectal cancer cases. microRNAs (miRNAs) regulate the expression of key genes in Wnt/βâcatenin signaling. As a result, abnormal expression of miRNAs regulates the activation of Wnt/βâcatenin signaling in several types of cancer. In the current study, it was demonstrated that miRâ501â3p was overexpressed in colorectal tumor tissues compared to the adjacent normal tissues. Downregulation of miRâ501â3p 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/βâcatenin signaling, was a potential target gene of miRâ501â3p. Inhibition of miRâ501â3p increased APC expression in colorectal cancer cells. Additionally, βâcatenin was destabilized following miRâ501â3p inhibition; immunofluorescence analysis revealed that βâcatenin translocated from nucleus to cytoplasm. In addition, cyclin D1 and câMyc, two wellâcharacterized target genes of Wnt/βâcatenin signaling, were downregulated following miRâ501â3p inhibition. Transfection of APC small interfering RNA reâactivated βâcatenin and stimulated the expression of cyclin D1 and câMyc. Furthermore, silencing of APC reversed the miRâ501â3p inhibitorâinduced cell cycle disruption, and the inhibition of cell proliferation and sphere formation in colorectal cancer cells. In conclusion, the present study identified miRâ501â3p as a novel regulator of Wnt/βâcatenin signaling in colorectal cancer cells via targeting APC, suggesting that miRâ501â3p may act as a novel oncogenic miRNA in colorectal cancer.
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