Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer
Shanghai Jiao Tong University · Shanghai First People's Hospital · +3 more institutions
Abstract
Abstract Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m 6 A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly…
Citation impact
- FWCI
- 58.44
- Percentile
- 100%
- References
- 70
Authors
13- LSLianhui SunCorresponding
Shanghai Jiao Tong University, Shanghai First People's Hospital, Shanghai Clinical Research Center
- YZYuan Zhang
Shanghai Jiao Tong University, Shanghai First People's Hospital
- BYBoyu Yang
Capital Medical University, Beijing Friendship Hospital
- SSSijun Sun
Shanghai Jiao Tong University, Shanghai First People's Hospital
- PZPengshan Zhang
Shanghai Jiao Tong University, Shanghai First People's Hospital
Topics & keywords
- Cancer research
- Cancer
- In vivo
- Chemistry
- Messenger RNA
- SIRT2
- In vitro
- Biology
- Good health and well-being