Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis.
Front Med
; 18(2): 344-356, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38466502
ABSTRACT
ALKBH5 is a master regulator of N6-methyladenosine (m6A) modification, which plays a crucial role in many biological processes. Here, we show that ALKBH5 is required for breast tumor growth. Interestingly, PRMT6 directly methylates ALKBH5 at R283, which subsequently promotes breast tumor growth. Furthermore, arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation, leading to increased aerobic glycolysis. Moreover, PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice. Collectively, these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arginine
/
Protein-Arginine N-Methyltransferases
/
Breast Neoplasms
/
AlkB Homolog 5, RNA Demethylase
/
Glycolysis
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Front Med
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
China