The demethylation of genes antagonized by TET1 in the regulation of the Wnt/β-catenin signaling pathway impacts the biological characteristics of colorectal cancer.

Abstract

Abstract The TET family is a ten-eleven translocation family of dioxygenases that oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and other oxidation products to regulate DNA methylation. Our data revealed significant downregulation of TET1 expression in CRC issues and SW480 cells. The database highlighted mutations as the primary mode of alteration of TET1 in CRC. The bioinformatics analysis results revealed a significant association between TET1 and immune cell infiltration, while indicating that the expression levels of immune checkpoint-related genes in CRC tissues tend to be elevated in comparison to normal tissues. Upon transfection, overexpression of TET1 exerted a comprehensive inhibitory effect by suppressing cell proliferation, inducing apoptosis, hindering migration and invasion, arresting cell cycle progression, and attenuating the activity of the Wnt/β-catenin signaling pathway as well as in nuclear β-catenin expression. Overexpression of TET1 increased 5hmC levels while simultaneously decreasing 5mC levels. We revealed antagonistic genes SFRP2 and WIF1 within the Wnt/β-catenin signaling pathway, which have a significant increase in expression level and a decrease in hypermethylation level upon TET1 overexpression. In conclusion, TET1 exerts its antitumor function by inhibiting the activity of Wnt/β-catenin signaling pathways through demethylation of the antagonistic genes SFRP2 and WIF1. This modulation has a significant impact on the biological properties of CRC.