Jingyu Chen, Lu Xu, Wangshi Li, Meiling Sun, Yao Chen, Ting Qiu, Yue Wu, Xingzhi Lv, Fukai Liu, Huitao Fan
{"title":"AKR1B1 is Required for Maintaining Acute Leukemia Cell Survival by Epigenetic Silencing of Tumor Suppressor Genes.","authors":"Jingyu Chen, Lu Xu, Wangshi Li, Meiling Sun, Yao Chen, Ting Qiu, Yue Wu, Xingzhi Lv, Fukai Liu, Huitao Fan","doi":"10.1007/s10528-024-10984-2","DOIUrl":null,"url":null,"abstract":"<p><p>AKR1B1 is a member of aldo-keto-reductase (AKR) superfamily which catalyze the reduction of carbonyl groups to hydroxyl groups in NADPH-dependent ways. Previous studies have shown that AKR1B1 promotes cancer progression, but its exact role in acute leukemia was unclear. Cell counting and Luminescent Cell Viability Assay were performed to measure the cell proliferation and viability. Soft-Agar Colony Formation (CFU) assay was conducted to measure the capacity of single cells to form colonies in vitro. Cell apoptosis, cell cycle, and cell differentiation were assessed by flow cytometry. Western blotting and RT-qPCR were utilized to examine AKR1B1 expression in acute leukemia cells. In vivo leukemia growth and mouse survival were evaluated using a model of xenotransplantation mice. We explored the AKR1B1 effect and mechanism in acute leukemia cells using RNA-sequencing technology and transcriptomic analysis. AKR1B1 is highly expressed in acute leukemia cells. Knockdown of AKR1B1 inhibited acute leukemia cell proliferation, colony-forming capability, and cell cycle and promoted apoptosis. Additionally, xenograft experiments proved that knockdown of AKR1B1 delayed the progression of acute leukemia cell in vivo. RNA-sequencing data analysis demonstrated that AKR1B1 was involved in the epigenetic silencing of H3K27me3-targeted genes. EZH2 inhibitor UNC1999 combined with knockdown of AKR1B1 showed synergistic inhibitory effect on acute leukemia cells. AKR1B1 is essential for the leukemogenesis and may serve as a potential therapeutic target to treat acute leukemia patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10528-024-10984-2","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
AKR1B1 is a member of aldo-keto-reductase (AKR) superfamily which catalyze the reduction of carbonyl groups to hydroxyl groups in NADPH-dependent ways. Previous studies have shown that AKR1B1 promotes cancer progression, but its exact role in acute leukemia was unclear. Cell counting and Luminescent Cell Viability Assay were performed to measure the cell proliferation and viability. Soft-Agar Colony Formation (CFU) assay was conducted to measure the capacity of single cells to form colonies in vitro. Cell apoptosis, cell cycle, and cell differentiation were assessed by flow cytometry. Western blotting and RT-qPCR were utilized to examine AKR1B1 expression in acute leukemia cells. In vivo leukemia growth and mouse survival were evaluated using a model of xenotransplantation mice. We explored the AKR1B1 effect and mechanism in acute leukemia cells using RNA-sequencing technology and transcriptomic analysis. AKR1B1 is highly expressed in acute leukemia cells. Knockdown of AKR1B1 inhibited acute leukemia cell proliferation, colony-forming capability, and cell cycle and promoted apoptosis. Additionally, xenograft experiments proved that knockdown of AKR1B1 delayed the progression of acute leukemia cell in vivo. RNA-sequencing data analysis demonstrated that AKR1B1 was involved in the epigenetic silencing of H3K27me3-targeted genes. EZH2 inhibitor UNC1999 combined with knockdown of AKR1B1 showed synergistic inhibitory effect on acute leukemia cells. AKR1B1 is essential for the leukemogenesis and may serve as a potential therapeutic target to treat acute leukemia patients.
期刊介绍：
Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses.
Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication.
Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses.
Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods.
Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
