{"title":"通过ybx1依赖性m5C修饰稳定CCT5 mRNA, NSUN2在肺腺癌中的致癌作用","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":"{\"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}","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}
The oncogenic role of NSUN2 in lung adenocarcinoma by stabilizing CCT5 mRNA via a YBX1-dependent m5C modification.
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.
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.