O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation.

IF 6.1 2区 生物学 Q1 CELL BIOLOGY
Yeolhoe Kim, Kyung-Tae Lee, Han Byeol Kim, Hyeryeon Jung, Jeong Yeon Ko, Tae Hyun Kweon, Hari Chandana Yadavalli, Junghwa Seo, Suena Ji, Yun Ju Kim, Donghyuk Shin, Seong Wook Yang, Myeong Min Lee, Jin Won Cho, Eugene C Yi, Jin-Wu Nam, Won Ho Yang
{"title":"O-GlcNAcylation of NONO regulates paraspeckle component assembly and contributes to colon cancer cell proliferation.","authors":"Yeolhoe Kim, Kyung-Tae Lee, Han Byeol Kim, Hyeryeon Jung, Jeong Yeon Ko, Tae Hyun Kweon, Hari Chandana Yadavalli, Junghwa Seo, Suena Ji, Yun Ju Kim, Donghyuk Shin, Seong Wook Yang, Myeong Min Lee, Jin Won Cho, Eugene C Yi, Jin-Wu Nam, Won Ho Yang","doi":"10.1038/s41420-025-02405-z","DOIUrl":null,"url":null,"abstract":"<p><p>Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"234"},"PeriodicalIF":6.1000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075841/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02405-z","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer.

NONO的o - glcn酰化调节斑点旁组分组装并促进结肠癌细胞增殖。
非pou结构域八聚体结合蛋白(NONO)是果蝇行为/人剪接(DBHS)蛋白家族的一个多功能成员,具有DNA和rna结合活性。NONO在各种类型的癌症中高度表达,过量的o - glcn酰化也与肿瘤发生有关。虽然最近的研究表明NONO被o - glcn酰化,并且这种修饰参与DNA损伤修复,但NONO的o - glcn酰化是否调节癌细胞增殖仍不清楚。此外,o - glcn酰化对NONO其他生物学特性的影响知之甚少。在这项研究中,我们确定了Thr440是主要的NONO- glcn酰化位点,并证明了它在哺乳动物细胞中促进NONO依赖性转录调控的重要亚核室paraspeckles组装中的关键作用。此外,我们发现NONO的o - glcn酰化对于维持参与有丝分裂的微管细胞骨架组织相关基因的表达以及抑制细胞对I型干扰素反应相关基因的表达是必需的。在这些基因的调控方面,在Thr440位点缺失NONO o - glcnac酰化可显著抑制结肠癌细胞的增殖。总的来说,我们的研究结果强调NONO o - glcn酰化是调节副斑形成的关键调节因子,也是结肠癌的候选治疗靶点。
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
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信