title: Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells.
abstract: A20, also known as tumor necrosis factor-α (TNFα)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors. However, little is known about the protein expression level and function of A20 in acute lymphoblastic leukemia (ALL). In this study, we found that A20 is up-regulated in ALL patients and several cell lines. Knockdown of A20 in Jurkat, Nalm-6, and Reh cells resulted in reduced cell proliferation, which was associated with cell cycle arrest. Phospho-ERK (p-ERK) was also down-regulated, while p53 and p21 were up-regulated in A20 knockdown cells. In addition, A20 knockdown induced apoptosis in Jurkat and Reh cells and enhanced the sensitivity of these cell lines to chemotherapeutic drugs. These results indicate that A20 may stimulate cell proliferation by regulating cell cycle progression. A20 inhibited apoptosis in some types of ALL cells, thereby enhancing their resistance to chemotherapy. This effect was abolished through A20 silencing. These findings suggest that A20 may contribute to the pathogenesis of ALL and that it may be used as a new therapeutic target for ALL treatment.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Shouyun
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Kejing
authors.initials: K
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Rao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China. Electronic address: wangjx@ihcams.ac.cn.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D048049:Extracellular Signal-Regulated MAP Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003630:Daunorubicin
keywords: A20; ALL; Apoptosis; Cell proliferation; Daunorubicin; Xenograft