Abnormal m6A modification in non-alcoholic fatty liver disease.

OBJECTIVES

Non-alcoholic fatty liver disease has seriously affected people's health. Recent studies have found that N6-methyladenosine (m6A) methylation is involved in the lipid metabolism process of the body, but the study on the level of m6A modification in NAFLD is still not available. This study aims to explore the changes in the level of RNA m6A methylation modification in NAFLD liver tissues, and to provide experimental and theoretical basis for in-depth study on the role of RNA m6A methylation in the occurrence and development of NAFLD.

METHODS

Changes in the m6A level in NAFLD liver tissues were measured by liquid chromatography-mass spectrometry (LC-MS). Total RNA was extracted from liver tissues of NAFLD patients or normal control individuals and subjected to methylated RNA immunoprecipitation (MeRIP) with microarray analysis (including 44 122 mRNAs and 12 496 lncRNAs) to determine the changes in m6A modification levels across the entire transcriptome. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to annotate the differentially modified mRNAs. Finally, 4 mRNAs and 4 lncRNAs were randomly selected to verify the microarray results by MeRIP and real-time transcription polymerase chain reaction.

RESULTS

A total of 176 mRNAs and 44 lncRNAs were found to be differentially m6A-modified in the NAFLD group compared with the control group. Among them, 15 mRNAs and 7 lncRNAs were hypermethylated in NAFLD, while 161 mRNAs and 37 lncRNAs were hypomethylated in NAFLD. GO and pathway analysis showed that the differentially modified mRNAs were enriched mainly in biological processes such as carboxylic acid metabolism and transcriptional regulation.

CONCLUSIONS

The m6A modification profile is changed in NAFLD liver tissues compared with normal liver tissues, which may functionally impact the pathophysiological progress in NAFLD.