H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3

IF 4.5 2区生物学 Q2 CELL BIOLOGY

Journal of Cellular Physiology Pub Date : 2024-08-07 DOI:10.1002/jcp.31402

Xinwei Hou, Yang Yang, Chen Wang, Zhaorong Huang, Mengzhen Zhang, Jiaming Yang, Nan Li, Huirong Yang, Liucheng Yang, Kai Wu

{"title":"H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3","authors":"Xinwei Hou, Yang Yang, Chen Wang, Zhaorong Huang, Mengzhen Zhang, Jiaming Yang, Nan Li, Huirong Yang, Liucheng Yang, Kai Wu","doi":"10.1002/jcp.31402","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n <p>The pathogenesis of Hirschsprung's disease (HSCR) is complex. Recently, it has been found that histone modifications can alter genetic susceptibility and play important roles in the proliferation, differentiation and migration of neural crest cells. H3K36 methylation plays a significant role in gene transcriptional activation and expression, but its pathogenic mechanism in HSCR has not yet been studied. This study aimed to elucidate its role and molecular mechanism in HSCR. Western blot analysis, immunohistochemistry (IHC) and reverse transcription-quantitative PCR (RT‒qPCR) were used to investigate H3K36 methylation and methyltransferase levels in dilated and stenotic colon tissue sections from children with. We confirm that SMYD2 is the primary cause of differential H3K36 methylation and influences cell proliferation and migration in HSCR. Subsequently, quantitative detection of m6A RNA methylation revealed that SMYD2 can alter m6A methylation levels. Western blot analysis, RT-qPCR, co-immunoprecipitation (co-IP), and immunofluorescence colocalization were utilized to confirm that SMYD2 can regulate METTL3 expression and affect m6A methylation, affecting cell proliferation and migration. These results confirm that the H3K36 methyltransferase SMYD2 can affect cell proliferation and migration in Hirschsprung's disease by regulating METTL3. Our study suggested that H3K36 methylation plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.</p>\n </section>\n </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 9","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cellular Physiology","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jcp.31402","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The pathogenesis of Hirschsprung's disease (HSCR) is complex. Recently, it has been found that histone modifications can alter genetic susceptibility and play important roles in the proliferation, differentiation and migration of neural crest cells. H3K36 methylation plays a significant role in gene transcriptional activation and expression, but its pathogenic mechanism in HSCR has not yet been studied. This study aimed to elucidate its role and molecular mechanism in HSCR. Western blot analysis, immunohistochemistry (IHC) and reverse transcription-quantitative PCR (RT‒qPCR) were used to investigate H3K36 methylation and methyltransferase levels in dilated and stenotic colon tissue sections from children with. We confirm that SMYD2 is the primary cause of differential H3K36 methylation and influences cell proliferation and migration in HSCR. Subsequently, quantitative detection of m6A RNA methylation revealed that SMYD2 can alter m6A methylation levels. Western blot analysis, RT-qPCR, co-immunoprecipitation (co-IP), and immunofluorescence colocalization were utilized to confirm that SMYD2 can regulate METTL3 expression and affect m6A methylation, affecting cell proliferation and migration. These results confirm that the H3K36 methyltransferase SMYD2 can affect cell proliferation and migration in Hirschsprung's disease by regulating METTL3. Our study suggested that H3K36 methylation plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.

查看原文本刊更多论文

H3K36甲基转移酶SMYD2通过调节METTL3影响赫氏麻风病的细胞增殖和迁移。

赫氏胃肠病（HSCR）的发病机制十分复杂。最近研究发现，组蛋白修饰可改变遗传易感性，并在神经嵴细胞的增殖、分化和迁移过程中发挥重要作用。H3K36 甲基化在基因转录激活和表达中起着重要作用，但其在 HSCR 中的致病机制尚未研究清楚。本研究旨在阐明其在 HSCR 中的作用和分子机制。本研究采用Western印迹分析、免疫组织化学（IHC）和逆转录定量PCR（RT-qPCR）技术研究了HSCR患儿扩张和狭窄结肠组织切片中H3K36甲基化和甲基转移酶水平。我们证实，SMYD2 是 H3K36 甲基化差异的主要原因，并影响 HSCR 的细胞增殖和迁移。随后，m6A RNA甲基化的定量检测显示，SMYD2可改变m6A甲基化水平。利用Western印迹分析、RT-qPCR、共免疫沉淀（co-IP）和免疫荧光共聚焦等方法证实，SMYD2能调控METTL3的表达并影响m6A甲基化，从而影响细胞的增殖和迁移。这些结果证实，H3K36甲基转移酶SMYD2可通过调控METTL3影响赫氏咽鼓管病的细胞增殖和迁移。我们的研究表明，H3K36甲基化在HSCR中起着重要作用，证实了甲基转移酶SMYD2可通过调控METTL3的表达影响m6A甲基化水平和肠神经系统的发育。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Cellular Physiology 生物-生理学

CiteScore

14.70

自引率

0.00%

发文量

256

审稿时长

1 months

期刊介绍： The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.