Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury
Fudan University · Sun Yat-sen University · +4 more institutions
Abstract
Elevated lactate levels are a significant biomarker of sepsis and are positively associated with sepsis-related mortality. Sepsis-associated lung injury (ALI) is a leading cause of poor prognosis in clinical patients. However, the underlying mechanisms of lactate's involvement in sepsis-associated ALI remain unclear. In this study, we demonstrate that lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300-mediated H3K18la binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in ACSL4, and its mRNA stability is regulated through a YTHDC1-dependent pathway. Furthermore, short-term lactate stimulation upregulates ACSL4, which promotes…
Citation impact
- FWCI
- 48.36
- Percentile
- 100%
- References
- 46
Authors
5- DWDan Wu
Fudan University, Sun Yat-sen University, Zhongshan Hospital, The First Affiliated Hospital, Sun Yat-sen University, Shanghai Medical College of Fudan University
- CBCharles B. Spencer
The Ohio State University
- LOLilibeth Ortoga
The Ohio State University
- HZHao ZhangCorresponding
Sun Yat-sen University, Shanghai Medical College of Fudan University, Fudan University, Zhongshan Hospital, The First Affiliated Hospital, Sun Yat-sen University
- CMChanghong MiaoCorresponding
The First Affiliated Hospital, Sun Yat-sen University, Sun Yat-sen University, Zhongshan Hospital, Shanghai Medical College of Fudan University, Fudan University
Topics & keywords
- Sepsis
- Gene knockdown
- Histone
- Cancer research
- Lung
- Medicine
- Cell biology
- Apoptosis
- Good health and well-being