The oncogenic role of NSUN2 in lung adenocarcinoma by stabilizing CCT5 mRNA via a YBX1-dependent m5C modification.

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Minxia Li, Ning Du, Ping Tang
{"title":"The oncogenic role of NSUN2 in lung adenocarcinoma by stabilizing CCT5 mRNA via a YBX1-dependent m5C modification.","authors":"Minxia Li, Ning Du, Ping Tang","doi":"10.1007/s11010-025-05378-w","DOIUrl":null,"url":null,"abstract":"<p><p>5-methylcytosine (m5C) methylation is a post-transcriptional modification of RNAs, and its dysregulation plays pro-tumorigenic roles in lung adenocarcinoma (LUAD). Here, this study elucidated the mechanism of action of NSUN2, a major m5C methyltransferase, on LUAD progression. mRNA expression was analyzed by quantitative PCR. Protein expression was tested by immunohistochemistry and immunoblotting. Cell proliferation was evaluated by MTT and EdU assays. Cell apoptosis was detected by flow cytometry and TUNEL staining. Transwell assays were used to examine cell invasion and migration. The influence of NSUN2 or the m5C reader YBX1 in CCT5 mRNA was analyzed by RNA immunoprecipitation assay and Actinomycin D treatment. In human LUAD, NSUN2 expression was upregulated, and high NSUN2 expression foreboded worse overall survival of LUAD patients. NSUN2 knockdown suppressed cell proliferation, diminished invasive and migratory potentials, and stimulated apoptosis in LUAD cells. NSUN2 was positively associated with CCT5 expression in LUAD and could mediate m5C modification of CCT5 mRNA. NSUN2 enhanced CCT5 mRNA stability and protein expression via two specific cysteines (C271 and C321). Moreover, YBX1 promoted CCT5 mRNA stability and protein expression. Additionally, restoration of CCT5 expression abolished NSUN2 deletion-mediated in vitro anti-proliferation, pro-apoptosis, anti-migration, and anti-invasiveness effects in LUAD cells, as well as in vivo anti-tumor growth behavior. Our study indicates that NSUN2 enhances the stability of CCT5 mRNA through a YBX1-m5C-dependent manner to drive LUAD progression. Targeting the NSUN2/CCT5 axis may be a potential approach to combat LUAD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05378-w","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

5-methylcytosine (m5C) methylation is a post-transcriptional modification of RNAs, and its dysregulation plays pro-tumorigenic roles in lung adenocarcinoma (LUAD). Here, this study elucidated the mechanism of action of NSUN2, a major m5C methyltransferase, on LUAD progression. mRNA expression was analyzed by quantitative PCR. Protein expression was tested by immunohistochemistry and immunoblotting. Cell proliferation was evaluated by MTT and EdU assays. Cell apoptosis was detected by flow cytometry and TUNEL staining. Transwell assays were used to examine cell invasion and migration. The influence of NSUN2 or the m5C reader YBX1 in CCT5 mRNA was analyzed by RNA immunoprecipitation assay and Actinomycin D treatment. In human LUAD, NSUN2 expression was upregulated, and high NSUN2 expression foreboded worse overall survival of LUAD patients. NSUN2 knockdown suppressed cell proliferation, diminished invasive and migratory potentials, and stimulated apoptosis in LUAD cells. NSUN2 was positively associated with CCT5 expression in LUAD and could mediate m5C modification of CCT5 mRNA. NSUN2 enhanced CCT5 mRNA stability and protein expression via two specific cysteines (C271 and C321). Moreover, YBX1 promoted CCT5 mRNA stability and protein expression. Additionally, restoration of CCT5 expression abolished NSUN2 deletion-mediated in vitro anti-proliferation, pro-apoptosis, anti-migration, and anti-invasiveness effects in LUAD cells, as well as in vivo anti-tumor growth behavior. Our study indicates that NSUN2 enhances the stability of CCT5 mRNA through a YBX1-m5C-dependent manner to drive LUAD progression. Targeting the NSUN2/CCT5 axis may be a potential approach to combat LUAD.

通过ybx1依赖性m5C修饰稳定CCT5 mRNA, NSUN2在肺腺癌中的致癌作用
5-甲基胞嘧啶(m5C)甲基化是rna的转录后修饰,其失调在肺腺癌(LUAD)中起促瘤作用。本研究阐明了主要的m5C甲基转移酶NSUN2在LUAD进展中的作用机制。定量PCR分析mRNA表达情况。免疫组织化学和免疫印迹法检测蛋白表达。MTT和EdU检测细胞增殖情况。流式细胞术、TUNEL染色检测细胞凋亡。Transwell法检测细胞侵袭和迁移。通过RNA免疫沉淀法和放线菌素D处理分析NSUN2或m5C读取器YBX1对CCT5 mRNA的影响。在人类LUAD中,NSUN2表达上调,NSUN2高表达预示着LUAD患者的总生存期较差。NSUN2敲低可抑制LUAD细胞的增殖,降低其侵袭和迁移潜能,并刺激细胞凋亡。NSUN2在LUAD中与CCT5表达呈正相关,可介导CCT5 mRNA的m5C修饰。NSUN2通过两种特定的半胱氨酸(C271和C321)增强CCT5 mRNA的稳定性和蛋白表达。此外,YBX1促进了CCT5 mRNA的稳定性和蛋白的表达。此外,CCT5表达的恢复消除了NSUN2缺失介导的LUAD细胞的体外抗增殖、促凋亡、抗迁移和抗侵袭作用,以及体内抗肿瘤生长行为。我们的研究表明,NSUN2通过ybx1 - m5c依赖的方式增强CCT5 mRNA的稳定性,从而驱动LUAD的进展。瞄准NSUN2/CCT5轴可能是对抗LUAD的一种潜在方法。
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
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
×
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