Novel insights into the role of N6-methyladenosine modification in regulating individual differences in hepatic drug metabolism
10.3867/j.issn.1000-3002.2025.08272
- VernacularTitle:N6-甲基腺苷修饰在调控肝药物代谢个体差异中的研究进展
- Author:
Haotian CHENG
1
;
Qinhao LI
;
Mingzhu LI
;
Pei WANG
Author Information
1. 郑州大学 基础医学院，河南 郑州 450001;郑州大学 第一临床医学院，河南 郑州 450001
- Publication Type:Journal Article
- Keywords:
N6-methyladenosine modification;
RNA modification;
drug-metabolizing enzymes;
indi-vidual difference
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(5):361-369
- CountryChina
- Language:Chinese
-
Abstract:
Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.
