Ten-Eleven Translocation 1 (TET1) is a member of methylcytosine dioxygenase, which catalyse 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) that promote the demethylation process. The diminished expression of TET1 protein and 5-hmC in many tumors indicate a critical role for the maintenance of cell stability. However, role of TET1 in bladder cancer development remains unclear. Here we found that TET1 expression was downregulated in bladder cancer tissues compared with normal urothelium and was inversely related to patient overall survival. TET1 silencing in bladder cancer cells increase proliferation and inhibited cell migration and invasion while its re-expression inhibits their proliferation and the growth of tumor xenografts.  Furthermore, we found that TET1 binds to the promoter of the TSG  to maintain its hypomethylated which interacts with -catenin and suppress its nuclear translocation, thus inhibiting -catenin transcriptional activity and downstream genes. In conclusion, TET1 acts as a tumor suppressor gene in bladder cancer cells by suppressing -catenin signaling. This study may facilitate efforts to therapeutic strategy for patients with bladder cancer. SOURCE: Yilin Yan (yyl718@sjtu.edu.cn) -  Shanghai General Hospital

Pluto Bioinformatics

GSE137646: TET1 is a tumour suppressor that inhibits bladder cancer progression