GSE136664 YTHDF1 Amplifies Wnt/ β-Catenin Signaling to Promote Intestinal Stemness

Contributors : Bing Han ; Saisai Wei ; Sujun Yan ; Tiezheng Li ; Jie Xiang ; Kangli Liu ; Rongpan Bai ; Jinghao Sheng ; Zhengping Xu ; Xiangwei GaoSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensWnt/ β-catenin signaling is essential for intestinal stem cell homeostasis and aberrant activation of this signaling leads to tumorigenesis. Here we report a function of YTHDF1, an mRNA m6A reader, in mediating β-catenin hyperactivation. Wnt signaling promotes YTHDF1 expression at the translational lev el. YTHDF1 is dispensable for normal intestinal development in mice while essential for intestinal regeneration. Ythdf1 knockout reduces the stemness of intestinal stem cells, which blocks Wnt-driven tumorigenesis. Genome-wide analysis identifies a subset of Wnt signaling components regulated by YTH DF1 in an m6A-dependent manner. Moreover, we demonstrate that YTHDF1 promotes the translation of TCF7L2/TCF4 to augment β-catenin activation. Targeting YTHDF1 in the established tumors leads to tumor shrinkage and prolonged survival. Together, our studies uncover YTHDF1 as an integral regulator of Wnt signaling at the translational level during intestinal tumorigenesis, which might serve as a promising target for colorectal cancer therapy.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research