Wu Duan, Ziyi Peng, Kun Yang, Mengyuan Hu, Xuefeng Yu, Benping Zhang, Li Liu
{"title":"1型糖尿病进展中转录组范围内n6 -甲基腺苷甲基化动态特征","authors":"Wu Duan, Ziyi Peng, Kun Yang, Mengyuan Hu, Xuefeng Yu, Benping Zhang, Li Liu","doi":"10.1080/17501911.2025.2510196","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>To map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D).</p><p><strong>Materials & methods: </strong>RNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis.</p><p><strong>Results: </strong>Bioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was \"GGACU\" in the control and pre-diabetes stages, shifting to \"GGACU/A\" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5.</p><p><strong>Conclusions: </strong>m6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-12"},"PeriodicalIF":3.0000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transcriptome-wide N6-methyladenosine methylation dynamic profile in type 1 diabetes progression.\",\"authors\":\"Wu Duan, Ziyi Peng, Kun Yang, Mengyuan Hu, Xuefeng Yu, Benping Zhang, Li Liu\",\"doi\":\"10.1080/17501911.2025.2510196\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>To map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D).</p><p><strong>Materials & methods: </strong>RNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis.</p><p><strong>Results: </strong>Bioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was \\\"GGACU\\\" in the control and pre-diabetes stages, shifting to \\\"GGACU/A\\\" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5.</p><p><strong>Conclusions: </strong>m6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.</p>\",\"PeriodicalId\":11959,\"journal\":{\"name\":\"Epigenomics\",\"volume\":\" \",\"pages\":\"1-12\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17501911.2025.2510196\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17501911.2025.2510196","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Transcriptome-wide N6-methyladenosine methylation dynamic profile in type 1 diabetes progression.
Aims: To map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D).
Materials & methods: RNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis.
Results: Bioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was "GGACU" in the control and pre-diabetes stages, shifting to "GGACU/A" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5.
Conclusions: m6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.
期刊介绍：
Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community.
Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.
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