Xiang Ma, Haodong Li, Ziqi Zhao, Changchun Li, Man Wang, Lele Zhang, Yutong Zhao, Haipeng Su, Feng Wang, Jiai Hua
{"title":"HNRNPC/CELF2信号通路在耐药急性髓性白血病中驱动糖解重编程和线粒体功能障碍。","authors":"Xiang Ma, Haodong Li, Ziqi Zhao, Changchun Li, Man Wang, Lele Zhang, Yutong Zhao, Haipeng Su, Feng Wang, Jiai Hua","doi":"10.1186/s13578-025-01386-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is an aggressive cancer with high treatment resistance, often leading to poor patient outcomes. Metabolic reprogramming plays a critical role in AML progression, influencing drug resistance (DR) and tumor survival. This study investigates the HNRNPC/CELF2 signaling pathway and its impact on AML cell metabolism and DR.</p><p><strong>Results: </strong>The study identified that HNRNPC regulates the expression of CELF2 through m6 A modification. In drug-resistant AML cells, increased HNRNPC expression and decreased CELF2 expression were associated with upregulated glycolysis, enhanced glucose consumption, lactate production, and mitochondrial dysfunction. Knockdown of HNRNPC reduced glycolysis and cell invasion, while CELF2 knockdown reversed these effects. Conversely, HNRNPC overexpression enhanced glycolysis and cell migration, which were counteracted by CELF2 overexpression.</p><p><strong>Conclusions: </strong>The HNRNPC/CELF2 axis plays a pivotal role in metabolic reprogramming, driving AML progression and chemotherapy resistance. Targeting this pathway may offer new therapeutic strategies to overcome resistance and improve treatment outcomes in AML patients.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"61"},"PeriodicalIF":6.1000,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083169/pdf/","citationCount":"0","resultStr":"{\"title\":\"The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia.\",\"authors\":\"Xiang Ma, Haodong Li, Ziqi Zhao, Changchun Li, Man Wang, Lele Zhang, Yutong Zhao, Haipeng Su, Feng Wang, Jiai Hua\",\"doi\":\"10.1186/s13578-025-01386-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is an aggressive cancer with high treatment resistance, often leading to poor patient outcomes. Metabolic reprogramming plays a critical role in AML progression, influencing drug resistance (DR) and tumor survival. This study investigates the HNRNPC/CELF2 signaling pathway and its impact on AML cell metabolism and DR.</p><p><strong>Results: </strong>The study identified that HNRNPC regulates the expression of CELF2 through m6 A modification. In drug-resistant AML cells, increased HNRNPC expression and decreased CELF2 expression were associated with upregulated glycolysis, enhanced glucose consumption, lactate production, and mitochondrial dysfunction. Knockdown of HNRNPC reduced glycolysis and cell invasion, while CELF2 knockdown reversed these effects. Conversely, HNRNPC overexpression enhanced glycolysis and cell migration, which were counteracted by CELF2 overexpression.</p><p><strong>Conclusions: </strong>The HNRNPC/CELF2 axis plays a pivotal role in metabolic reprogramming, driving AML progression and chemotherapy resistance. Targeting this pathway may offer new therapeutic strategies to overcome resistance and improve treatment outcomes in AML patients.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"15 1\",\"pages\":\"61\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083169/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-025-01386-x\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-025-01386-x","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia.
Background: Acute myeloid leukemia (AML) is an aggressive cancer with high treatment resistance, often leading to poor patient outcomes. Metabolic reprogramming plays a critical role in AML progression, influencing drug resistance (DR) and tumor survival. This study investigates the HNRNPC/CELF2 signaling pathway and its impact on AML cell metabolism and DR.
Results: The study identified that HNRNPC regulates the expression of CELF2 through m6 A modification. In drug-resistant AML cells, increased HNRNPC expression and decreased CELF2 expression were associated with upregulated glycolysis, enhanced glucose consumption, lactate production, and mitochondrial dysfunction. Knockdown of HNRNPC reduced glycolysis and cell invasion, while CELF2 knockdown reversed these effects. Conversely, HNRNPC overexpression enhanced glycolysis and cell migration, which were counteracted by CELF2 overexpression.
Conclusions: The HNRNPC/CELF2 axis plays a pivotal role in metabolic reprogramming, driving AML progression and chemotherapy resistance. Targeting this pathway may offer new therapeutic strategies to overcome resistance and improve treatment outcomes in AML patients.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
