{"title":"m5C甲基转移酶NSUN2通过调节丝氨酸代谢促进急性髓系白血病的进展。","authors":"Songyu Li, Ya Liu, Xiang Wu, Minjia Pan, Hongxia Zhao, Yunguang Hong, Qinghua Zhang, Shushu Hu, Aorong Ouyang, Guangru Li, Minhui Wu, Shanshan Fan, Zhirong Jia, Shanchao Zhao, Guocai Wu, Xiangwei Gao, Zhigang Yang, Zhanghui Chen","doi":"10.1016/j.celrep.2025.115661","DOIUrl":null,"url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is one of the most prevalent heterogeneous hematologic malignancies with a complicated etiology. RNA post-transcriptional modifications have been linked to the incidence and progression of AML, while the detailed mechanism remains to be elucidated. In this study, we find that NOP2/Sun domain family member 2 (NSUN2), a methyltransferase of 5-methylcytosine (m<sup><sup>5</sup></sup>C) RNA methylation, is upregulated in AML and predicts a poor prognosis for patients with AML. Knockdown of NSUN2 in AML cells inhibits proliferation and colony formation and promotes apoptosis. Depletion of NSUN2 in AML mice reduces the tumor burden and prolongs survival. Mechanistically, NSUN2 promotes the expression of phosphoglycerate dehydrogenase (PHGDH) and serine hydroxymethyltransferase 2 (SHMT2), two key enzymes in the serine/glycine biosynthesis pathway, by stabilizing the corresponding mRNAs through regulation of m<sup>5</sup>C modifications. Overall, our findings demonstrate a critical role of NSUN2 in AML development and highlight the therapeutic potential of targeting the NSUN2/m<sup><sup>5</sup></sup>C axis for the treatment of this cancer.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115661"},"PeriodicalIF":7.5000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The m<sup><sup>5</sup></sup>C methyltransferase NSUN2 promotes progression of acute myeloid leukemia by regulating serine metabolism.\",\"authors\":\"Songyu Li, Ya Liu, Xiang Wu, Minjia Pan, Hongxia Zhao, Yunguang Hong, Qinghua Zhang, Shushu Hu, Aorong Ouyang, Guangru Li, Minhui Wu, Shanshan Fan, Zhirong Jia, Shanchao Zhao, Guocai Wu, Xiangwei Gao, Zhigang Yang, Zhanghui Chen\",\"doi\":\"10.1016/j.celrep.2025.115661\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute myeloid leukemia (AML) is one of the most prevalent heterogeneous hematologic malignancies with a complicated etiology. RNA post-transcriptional modifications have been linked to the incidence and progression of AML, while the detailed mechanism remains to be elucidated. In this study, we find that NOP2/Sun domain family member 2 (NSUN2), a methyltransferase of 5-methylcytosine (m<sup><sup>5</sup></sup>C) RNA methylation, is upregulated in AML and predicts a poor prognosis for patients with AML. Knockdown of NSUN2 in AML cells inhibits proliferation and colony formation and promotes apoptosis. Depletion of NSUN2 in AML mice reduces the tumor burden and prolongs survival. Mechanistically, NSUN2 promotes the expression of phosphoglycerate dehydrogenase (PHGDH) and serine hydroxymethyltransferase 2 (SHMT2), two key enzymes in the serine/glycine biosynthesis pathway, by stabilizing the corresponding mRNAs through regulation of m<sup>5</sup>C modifications. Overall, our findings demonstrate a critical role of NSUN2 in AML development and highlight the therapeutic potential of targeting the NSUN2/m<sup><sup>5</sup></sup>C axis for the treatment of this cancer.</p>\",\"PeriodicalId\":9798,\"journal\":{\"name\":\"Cell reports\",\"volume\":\"44 5\",\"pages\":\"115661\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell reports\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.celrep.2025.115661\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2025.115661","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The m5C methyltransferase NSUN2 promotes progression of acute myeloid leukemia by regulating serine metabolism.
Acute myeloid leukemia (AML) is one of the most prevalent heterogeneous hematologic malignancies with a complicated etiology. RNA post-transcriptional modifications have been linked to the incidence and progression of AML, while the detailed mechanism remains to be elucidated. In this study, we find that NOP2/Sun domain family member 2 (NSUN2), a methyltransferase of 5-methylcytosine (m5C) RNA methylation, is upregulated in AML and predicts a poor prognosis for patients with AML. Knockdown of NSUN2 in AML cells inhibits proliferation and colony formation and promotes apoptosis. Depletion of NSUN2 in AML mice reduces the tumor burden and prolongs survival. Mechanistically, NSUN2 promotes the expression of phosphoglycerate dehydrogenase (PHGDH) and serine hydroxymethyltransferase 2 (SHMT2), two key enzymes in the serine/glycine biosynthesis pathway, by stabilizing the corresponding mRNAs through regulation of m5C modifications. Overall, our findings demonstrate a critical role of NSUN2 in AML development and highlight the therapeutic potential of targeting the NSUN2/m5C axis for the treatment of this cancer.
期刊介绍：
Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership.
The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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