N 6-methyladenosine (m 6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year.
There are various cells in bladder tumor bulk, and a small population cells defined as tumor initiating cells (TIC) have self-renewal and differentiation capacities. Bladder TICs drive bladder tumorigenesis and metastasis, and their activities are fine regulated. However, the role of N 6-methyladenosine in bladder TIC self-renewal is unknown.
Here, we found a decrease of N 6-methyladenosine in bladder tumors and bladder TICs. N 6-methyladenosine levels are related to clinical severity and outcome. Mettl14 is lowly expressed in bladder cancer and bladder TICs. Mettl14 knockout promotes the proliferation, self-renewal, metastasis and tumor initiating capacity of bladder TICs, and Mettl14 overexpression exerts an opposite role. Mettl14 and m 6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m 6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal.