{"title":"HDAC2-miR183-5p 表观遗传回路通过 PTEN/AKT 和 c-MYC 信号通路促进费城染色体阳性 B 细胞急性淋巴细胞白血病的生长","authors":"Yangyang Ding,Xiangjiang Feng,Zelin Liu,Ya Liao,Lianfang Pu,Jun Liu,Huiping Wang,Zhimin Zhai,Shudao Xiong","doi":"10.1093/jleuko/qiae200","DOIUrl":null,"url":null,"abstract":"Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph(+)B-ALL) is a hematological malignancy with a poor prognosis. Epigenetic abnormalities, especially abnormal histone acetylation and microRNAs (miRNAs) dysregulation, are a group of epigenetic patterns that contribute to leukemia progression. However, their regulatory mechanisms in Ph(+)B-ALL have not been fully elucidated. In this study, we identified that miR-183-5p is significantly downregulated in Ph(+)B-ALL and associated with poor prognosis. Moreover, we found that the BCR-ABL fusion gene is a key target gene of miR-183-5p. MiR-183-5p directly targets BCR-ABL gene and induces cell apoptosis via PTEN/AKT and c-MYC signaling pathways. In addition, histone deacetylase inhibitor (HADCi) could mitigate the suppressive effects of HDAC2 on miR-183-5p by promoting promoter acetylation, thereby enhancing cell apoptosis. In conclusion, our results indicate that miR-183-5p is a potential biomarker and suggest that a novel \"HDAC2-miR-183-5p epigenetic circuitry regulation\" may be involved in the pathogenesis of Ph(+)B-ALL. Taken together, These findings provide new insights into the design of promising molecular-targeted drugs for Ph(+)B-ALL.","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HDAC2-miR183-5p Epigenetic Circuit Contributes to the Growth of Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia via PTEN/AKT and c-MYC Signaling Pathway.\",\"authors\":\"Yangyang Ding,Xiangjiang Feng,Zelin Liu,Ya Liao,Lianfang Pu,Jun Liu,Huiping Wang,Zhimin Zhai,Shudao Xiong\",\"doi\":\"10.1093/jleuko/qiae200\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph(+)B-ALL) is a hematological malignancy with a poor prognosis. Epigenetic abnormalities, especially abnormal histone acetylation and microRNAs (miRNAs) dysregulation, are a group of epigenetic patterns that contribute to leukemia progression. However, their regulatory mechanisms in Ph(+)B-ALL have not been fully elucidated. In this study, we identified that miR-183-5p is significantly downregulated in Ph(+)B-ALL and associated with poor prognosis. Moreover, we found that the BCR-ABL fusion gene is a key target gene of miR-183-5p. MiR-183-5p directly targets BCR-ABL gene and induces cell apoptosis via PTEN/AKT and c-MYC signaling pathways. In addition, histone deacetylase inhibitor (HADCi) could mitigate the suppressive effects of HDAC2 on miR-183-5p by promoting promoter acetylation, thereby enhancing cell apoptosis. In conclusion, our results indicate that miR-183-5p is a potential biomarker and suggest that a novel \\\"HDAC2-miR-183-5p epigenetic circuitry regulation\\\" may be involved in the pathogenesis of Ph(+)B-ALL. Taken together, These findings provide new insights into the design of promising molecular-targeted drugs for Ph(+)B-ALL.\",\"PeriodicalId\":16186,\"journal\":{\"name\":\"Journal of Leukocyte Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Leukocyte Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jleuko/qiae200\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Leukocyte Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jleuko/qiae200","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
HDAC2-miR183-5p Epigenetic Circuit Contributes to the Growth of Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia via PTEN/AKT and c-MYC Signaling Pathway.
Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph(+)B-ALL) is a hematological malignancy with a poor prognosis. Epigenetic abnormalities, especially abnormal histone acetylation and microRNAs (miRNAs) dysregulation, are a group of epigenetic patterns that contribute to leukemia progression. However, their regulatory mechanisms in Ph(+)B-ALL have not been fully elucidated. In this study, we identified that miR-183-5p is significantly downregulated in Ph(+)B-ALL and associated with poor prognosis. Moreover, we found that the BCR-ABL fusion gene is a key target gene of miR-183-5p. MiR-183-5p directly targets BCR-ABL gene and induces cell apoptosis via PTEN/AKT and c-MYC signaling pathways. In addition, histone deacetylase inhibitor (HADCi) could mitigate the suppressive effects of HDAC2 on miR-183-5p by promoting promoter acetylation, thereby enhancing cell apoptosis. In conclusion, our results indicate that miR-183-5p is a potential biomarker and suggest that a novel "HDAC2-miR-183-5p epigenetic circuitry regulation" may be involved in the pathogenesis of Ph(+)B-ALL. Taken together, These findings provide new insights into the design of promising molecular-targeted drugs for Ph(+)B-ALL.
期刊介绍:
JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.