Fig. 2: Wnt signaling induces the binding of EZH2 to β-catenin, leading to increased H3K27me3 in the FTO promoter region and subsequent inhibition of FTO expression. | Cell Death & Disease

Fig. 2: Wnt signaling induces the binding of EZH2 to β-catenin, leading to increased H3K27me3 in the FTO promoter region and subsequent inhibition of FTO expression.

From: WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis

Fig. 2

A H322 cells were treated with or without Wnt-3a for 8 h. ChIP analyses using an anti-TCF4 antibody and qPCR with the primer against the FTO promoter regions were performed. Data represent the means ± SD of triplicate samples. *P < 0.05. B A luciferase reporter vector with a WT or truncated FTO promoter was stably expressed in 293T cells. These cells were transfected with a control vector or a vector expressing active β-catenin. Relative luciferase activities were determined. ΔTBE1–3: deletion of the three TBEs in the FTO promoter. Data represent the means ± SD of triplicate samples. *P < 0.05. C, D H322 and H358 cells with or without β-catenin depletion were treated with or without Wnt-3a for 8 h. FTO mRNA (C) and protein (D) expression was determined by qPCR and immunoblotting analyses with the indicated antibodies, respectively. Data represent the means ± SD of triplicate samples. *P < 0.05, **P < 0.01, and ***P < 0.001. E H322 cells were treated with or without Wnt-3a for 8 h, ChIP analyses using an anti-H3K27me3 antibody and qPCR with the primer against the FTO promoter regions were performed. Data represent the means ± SD of triplicate samples. **P < 0.01. F H322 cells were treated with or without Wnt-3a for 8 h. Immunoprecipitation and immunoblotting analyses were performed with the indicated antibodies. G H322 cells were treated with or without Wnt-3a for 8 h. ChIP analyses using an anti-EZH2 antibody and qPCR with the primer against the FTO promoter regions were performed. Data represent the means ± SD of triplicate samples. **P < 0.01. H H322 and H358 cells with or without EZH2 depletion were stimulated with or without Wnt-3a for 8 h. Immunoblotting analyses were performed with the indicated antibodies. I The correlation of the mRNA levels of FTO with the mRNA levels of FZD9, DVL1, APC, GSK3β, and AXIN2 was analyzed in lung adenocarcinoma (n = 513) from the TCGA cohort. Pearson’s correlation test was used (two-tailed).

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