ZNF425基因抑制急性T淋巴细胞白血病细胞的凋亡
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摘要
为了解锌指(Zinc finger,ZNF)基因在癌症发生中的作用,利用生物信息学在CCLE数据库中分析得到ZNF425在白血病细胞系中存在高表达;在COSMIC和ICGC数据库中发现ZNF425在癌症患者的造血和淋巴组织中发生突变,并且表达存在差异。在急性T淋巴细胞白血病Jurkat细胞系瞬时过表达ZNF425,能抑制Jurkat细胞凋亡但Jurkat的细胞周期却不受影响,Western Blot检测发现过表达ZNF425导致ERK活化受到抑制。本研究结果首次揭示了ZNF425在血癌细胞中的功能,可能通过影响癌症细胞的凋亡调节癌症的发生。
To study the role of zinc finger( ZNF) genes in cancer developments,in this study,we made use of bioinformatics database and discovered that from the CCLE data analysis ZNF425 was highly expressed in leukemia cell lines. Analyses from COSMIC and ICGC data bases exhibited that ZNF425 was mutated in hematopoietic and lymphatic tissues of cancer patients and that expression levels of ZNF425 were different. Transient expressions of ZNF425 in acute T lymphocytic leukemia Jurkat cell lines can inhibit cells apoptosis but do not impact the cell cycle. Western blot detection results revealed that overexpression of ZNF425 inhibited pERK activation. For the first time,our results from the present study unveiled the function of ZNF425 in blood cancer cells. These results will shed new light on how to regulate the occurrence of cancer by affecting the apoptosis of cancer cells.
To study the role of zinc finger( ZNF) genes in cancer developments,in this study,we made use of bioinformatics database and discovered that from the CCLE data analysis ZNF425 was highly expressed in leukemia cell lines. Analyses from COSMIC and ICGC data bases exhibited that ZNF425 was mutated in hematopoietic and lymphatic tissues of cancer patients and that expression levels of ZNF425 were different. Transient expressions of ZNF425 in acute T lymphocytic leukemia Jurkat cell lines can inhibit cells apoptosis but do not impact the cell cycle. Western blot detection results revealed that overexpression of ZNF425 inhibited pERK activation. For the first time,our results from the present study unveiled the function of ZNF425 in blood cancer cells. These results will shed new light on how to regulate the occurrence of cancer by affecting the apoptosis of cancer cells.
引文
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[20]LIU J,LU W,LIU S,et al.ZFP36L2,a novel AML1 target gene,induces AML cells apoptosis and inhibits cell proliferation[J].Leukemia Res,2018,68:15.
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[23]SUI X,KONG N,YE L,et al.p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents[J].Cancer Lett,2014,344(2):174-179.
[24]SUN Y,LIU W Z,LIU T,et al.Signaling pathway of MAPK/ERK in cell proliferation,differentiation,migration,senescence and apoptosis[J].J Recept Sig Transd Res,2015,35(6):1-5.
[25]LI Q,HUAI L,ZHANG C,et al.Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways[J].Int J Hematol,2013,97(5):617-623.
[2]LACHENMANN M J,LADBURY J E,DONG J,et al.Why zinc fingers prefer zinc:ligand-field symmetry and the hidden thermodynamics of metal ion selectivity[J].Biochemistry,2004,43(44):13910-13925.
[3]WITZGALL R,O'LEARY E,LEAF A,et al.The Kruppel-associated box-A(KRAB-A)domain of zinc finger proteins mediates transcriptional repression.[J].Proc Natl Acad Sci USA,1994,91(10):4514-4518.
[4]CHAN D,WILSON T J,XU D,et al.Transformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1[J].Bri J Cancer,2003,88(1):137-145.
[5]JHEON A H.Characterization of a novel KRAB/C2H2zinc finger transcription factor involved in bone development[J].J Biol Chem,2001,276(21):18282-18289.
[6]KATOH O,OGURI T,TAKAHASHI T,et al.ZK1,a novel Krüppel-type zinc finger gene,is induced following exposure to ionizing radiation and enhances apoptotic cell death on hematopoietic cells[J].Biochem Biophys Res Commun,1998,249(3):595-600.
[7]SHEN Z,ASA S L,EZZAT S.The retrotransposon gag domain containing protein Rgag4 is an Ikaros target in the pituitary[J].Mol Cell Endocrinol,2017:S0303720717304987.
[8]WANG Y,YE X,ZHOU J,et al.A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway[J].Bmb Reports,2011,44(1):58.
[9]GREAVES M.Childhood leukaemia[J].BMJ,2002,324(7332):283-287.
[10]BHOJWANI D,PUI C H.Relapsed childhood acute lymphoblastic leukaemia[J].Lancet Oncol,2013,14(6):e205-e217.
[11]MARIA M,EMANUELA C,STEFANIA S,et al.ZNF423 and ZNF521:EBF1 antagonists of potential relevance in b-Lymphoid malignancies[J].Bio Med Res Int,2015,2015:1-9.
[12]TAO Y F,HU S Y,LU J,et al.Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients[J].Int J Mol Med,2014,34(6):1505-1515.
[13]MCNAMARA A R,FORD K G.A novel four zinc-finger protein targeted against p190BcrAbl fusion oncogene c DNA:utilisation of,zinc-finger recognition codes[J].Nucleic Acids Res,2000,28(24):4865-72.
[14]GAETANO S,GIANCARLO B,FEDERICA F,et al.ZNF224 is a transcriptional repressor of AXL in chronic myeloid leukemia cells[J].Biochimie,2018,154:127-131.
[15]王磊.表观遗传学在肿瘤中的研究进展[J].世界复合医学,2016,2(1):69-72.
[16]宋乔,高世超,王培昌.DNA甲基化的分子机制及其研究进展[J].基因组学与应用生物学:1-12.
[17]张艳超,任立红.甲基化与儿童急性淋巴细胞性白血病的相关性[J].中国小儿血液与肿瘤杂志,2016,21(2):108-109.
[18]BUCK-KOEHNTOP B A,STANFIELD R L,EKIERT D C,et al.Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso[J].Proc Natl Acad Sci USA,2012,109(38):15229-15234.
[19]BUSIELLO T,CIANO M,ROMANO S,et al.Role of ZNF224 in cell growth and chemoresistance of chronic lymphocitic leukemia[J].Human Mol Genet,2016:ddw427.
[20]LIU J,LU W,LIU S,et al.ZFP36L2,a novel AML1 target gene,induces AML cells apoptosis and inhibits cell proliferation[J].Leukemia Res,2018,68:15.
[21]ESPINOZA J L,ELBADRY M I,TANIWAKI M,et al.The simultaneous inhibition of the m TOR and MAPK pathways with Gnetin-C induces apoptosis in acute myeloid leukemia[J].Cancer Lett,2017:S0304383517302884.
[22]STIEGLITZ E,TAYLORWEINER A N,CHANG T Y,et al.The genomic landscape of juvenile myelomonocytic leukemia[J].Nat Genet,2015,47(11):1326-1333.
[23]SUI X,KONG N,YE L,et al.p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents[J].Cancer Lett,2014,344(2):174-179.
[24]SUN Y,LIU W Z,LIU T,et al.Signaling pathway of MAPK/ERK in cell proliferation,differentiation,migration,senescence and apoptosis[J].J Recept Sig Transd Res,2015,35(6):1-5.
[25]LI Q,HUAI L,ZHANG C,et al.Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways[J].Int J Hematol,2013,97(5):617-623.