Abnormal M6A Modification in Non-alcoholic Fatty Liver Disease

Overview

Journal Zhong Nan Da Xue Xue Bao Yi Xue Ban

Specialty General Medicine

Date 2021 Sep 27

PMID 34565720

Citations 2

Authors

Zhenzhou Li

Jing Qi

Huaizheng Liu

Yishu Tang

Jun Liu

Chuanzheng Sun

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

M6A methyltransferase METTL3 promotes glucose metabolism hub gene expression and induces metabolic dysfunction-associated steatotic liver disease (MASLD).

Wang S, Xu Z, Wang Z, Yi X, Wu J BMC Genomics. 2025; 26(1):188.

PMID: 39994526 PMC: 11853331. DOI: 10.1186/s12864-025-11377-4.

METTL3 promotes the progression of non-alcoholic fatty liver disease by mediating m6A methylation of FAS.

Li Q, Xiang J Sci Rep. 2025; 15(1):6162.

PMID: 39979577 PMC: 11842791. DOI: 10.1038/s41598-025-90419-z.

Regulatory roles of N6-methyladenosine (mA) methylation in RNA processing and non-communicable diseases.

Khan F, Nsengimana B, Awan U, Ji X, Ji S, Dong J Cancer Gene Ther. 2024; 31(10):1439-1453.

PMID: 38839892 DOI: 10.1038/s41417-024-00789-1.

New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC.

Cheng W, Li M, Zhang L, Zhou C, Yu S, Peng X Front Pharmacol. 2022; 13:973116.

PMID: 36120320 PMC: 9471244. DOI: 10.3389/fphar.2022.973116.

References

Luo Q, Gao Y, Zhang L, Rao J, Guo Y, Huang Z . Decreased , , and in Peripheral Blood Are as Risk Factors for Rheumatoid Arthritis. Biomed Res Int. 2020; 2020:5735279. PMC: 7455827. DOI: 10.1155/2020/5735279. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Mo X, Zhang Y, Lei S . Genome-wide identification of mA-associated SNPs as potential functional variants for bone mineral density. Osteoporos Int. 2018; 29(9):2029-2039. DOI: 10.1007/s00198-018-4573-y. View

Wang J, Wang K, Liu W, Cai Y, Jin H . m6A mRNA methylation regulates the development of gestational diabetes mellitus in Han Chinese women. Genomics. 2021; 113(3):1048-1056. DOI: 10.1016/j.ygeno.2021.02.016. View

Boccaletto P, Machnicka M, Purta E, Piatkowski P, Baginski B, Wirecki T . MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2017; 46(D1):D303-D307. PMC: 5753262. DOI: 10.1093/nar/gkx1030. View

Yan T, Wang H, Cao L, Wang Q, Takahashi S, Yagai T . Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation. Drug Metab Dispos. 2018; 46(9):1310-1319. PMC: 6081736. DOI: 10.1124/dmd.118.082008. View

Wehbe Z, Behringer S, Alatibi K, Watkins D, Rosenblatt D, Spiekerkoetter U . The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism. Biochim Biophys Acta Mol Cell Biol Lipids. 2019; 1864(11):1629-1643. DOI: 10.1016/j.bbalip.2019.07.012. View

Zhao X, Yang Y, Sun B, Shi Y, Yang X, Xiao W . FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014; 24(12):1403-19. PMC: 4260349. DOI: 10.1038/cr.2014.151. View

Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S . Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012; 485(7397):201-6. DOI: 10.1038/nature11112. View

10.

Mo X, Lei S, Zhang Y, Zhang H . Examination of the associations between mA-associated single-nucleotide polymorphisms and blood pressure. Hypertens Res. 2019; 42(10):1582-1589. DOI: 10.1038/s41440-019-0277-8. View

11.

Mo X, Lei S, Zhang Y, Zhang H . Genome-wide enrichment of mA-associated single-nucleotide polymorphisms in the lipid loci. Pharmacogenomics J. 2018; 19(4):347-357. DOI: 10.1038/s41397-018-0055-z. View

12.

Zhu R, Tian D, Zhao Y, Zhang C, Liu X . Genome-Wide Detection of mA-Associated Genetic Polymorphisms Associated with Ischemic Stroke. J Mol Neurosci. 2021; 71(10):2107-2115. DOI: 10.1007/s12031-021-01805-x. View

13.

Gao X, Fan J . Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology. J Diabetes. 2013; 5(4):406-15. PMC: 3933762. DOI: 10.1111/1753-0407.12056. View

14.

Dixit D, Prager B, Gimple R, Poh H, Wang Y, Wu Q . The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells. Cancer Discov. 2020; 11(2):480-499. PMC: 8110214. DOI: 10.1158/2159-8290.CD-20-0331. View

15.

Aramsangtienchai P, Spiegelman N, He B, Miller S, Dai L, Zhao Y . HDAC8 Catalyzes the Hydrolysis of Long Chain Fatty Acyl Lysine. ACS Chem Biol. 2016; 11(10):2685-2692. PMC: 5305809. DOI: 10.1021/acschembio.6b00396. View

16.

Luo Z, Zhang Z, Tai L, Zhang L, Sun Z, Zhou L . Comprehensive analysis of differences of N-methyladenosine RNA methylomes between high-fat-fed and normal mouse livers. Epigenomics. 2019; 11(11):1267-1282. DOI: 10.2217/epi-2019-0009. View

17.

Wang H, Xu B, Shi J . N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2. Gene. 2019; 722:144076. DOI: 10.1016/j.gene.2019.144076. View

18.

Xie W, Ma L, Xu Y, Wang B, Li S . METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019; 518(1):120-126. DOI: 10.1016/j.bbrc.2019.08.018. View

19.

Sun Y, Huang J, Chen Z, Du M, Ren F, Luo J . Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL/6 J Mice. J Nutr. 2019; 150(2):294-302. DOI: 10.1093/jn/nxz236. View

20.

Robinson M, Shah P, Cui Y, He Y . The Role of Dynamic m A RNA Methylation in Photobiology. Photochem Photobiol. 2018; 95(1):95-104. PMC: 6309319. DOI: 10.1111/php.12930. View