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LSD1和KDM5家族在卵巢癌细胞中的表达及LSD1对细胞增殖迁移的影响
作者:贾超1 2  王洁3  邵根宝3  陆祖宏1 
单位:1. 东南大学生物科学与医学工程学院 生物电子学国家重点实验室, 江苏 南京 210096;
2. 南京农业大学 动物科技学院, 江苏 南京 210095;
3. 江苏大学 医学院, 江苏 镇江 212013
关键词:赖氨酸特异去甲基化酶 卵巢癌 细胞增殖 细胞迁移 
分类号:R737.31;R73-3
出版年·卷·期(页码):2016·35·第三期(350-354)
摘要:

目的:研究赖氨酸特异去甲基化酶1(LSD1)和赖氨酸去甲基化酶5家族(KDM5家族成员)在人卵巢癌细胞中的表达,分析LSD1对细胞增殖迁移的影响。方法:在3种卵巢癌细胞株中,分别用RT-PCR检测LSD1、KDM5A、KDM5B、KDM5C、KDM5D的mRNA的表达,蛋白质印迹法检测前4种酶的表达;在人正常卵巢上皮细胞和癌细胞株中,采用蛋白质印迹法检测LSD1的表达;用MTT法检测LSD1对卵巢癌细胞株增殖的影响;应用划痕试验检测LSD1对卵巢癌细胞株迁移的影响。结果:在3种人卵巢癌细胞的上述5种酶中,LSD1表达水平最高(P<0.01),KDM5家族成员在不同细胞系中差异表达。LSD1抑制剂反苯环丙胺处理卵巢癌细胞后,用MTT法发现抑制LSD1能显著降低癌细胞增殖(P<0.05),刮痕实验发现该药物可显著抑制卵巢癌细胞的迁移(P<0.05)。结论:LSD1在卵巢癌中高表达,KDM5家族差异化表达;LSD1与卵巢癌细胞系的增殖和迁移能力密切相关。

Objective:To investigate the expression of lysine-specific demethylase 1(LSD1) and lysine demethylase 5 (KDM5), as well as the role of LSD1 on proliferation and migration within human ovarian cancer cells. Methods:Relative mRNA and protein levels of LSD1, KDM5A, KDM5B, KDM5C, KDM5D were detected respectively by real-time quantitative and Western blot in SKOV-3, HO8910, 3AO cells. The expressions of LSD1 were comparatively analyzed between a human ovarian epithelial cell line and three ovarian cancer cell lines by Western blot. In addition, the effects of LSD1 on proliferation and migration were determinted by MTT and wound-healing assay respectively. Results:The expression of LSD1 was highest(P<0.01), and the expression of KDM5 members was different in these ovarian cancer cells. Tranylcypromine, the inhibitor of LSD1, significantly decreased the proliferation and migration(P<0.05). Conclusion:LSD1 expresse at high level and the member of KDM5 family expresse at differentiated level within 3 ovarian cancer cell lines, and LSD1 is significantly correlated with the proliferation and migration within these 3 ovarian cancer cell lines.

参考文献:

[1] MCGRATH J,TROJER P.Targeting histone lysine methylation in cancer[J].Pharmacol Ther,2015,150:1-22.
[2] VARIER R A,TIMMERS H T.Histone lysine methylation and demethylation pathways in cancer[J].Biochim Biophys Acta,2011,1815(1):75-89.
[3] THINNES C C,ENGLAND K S,KAWAMURA A,et al.Targeting histone lysine demethylases-progress,challenges,and the future[J].Biochim Biophys Acta,2014,1839(12):1416-1432.
[4] LAN F,NOTTKE A C,SHI Y,Mechanisms involved in the regulation of histone lysine demethylases[J].Curr Opin Cell Biol,2008,20(3):316-325.
[5] ROTILI D,MAI A.Targeting histone demethylases:a new avenue for the fight against cancer[J].Genes Cancer,2011,2(6):663-679.
[6] SHAO G,WANG J,LI Y,et al.Lysine-specific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells[J].Sci Rep,2015,5:15344.
[7] ZHENG Y C,MA J,WANG Z,et al.A systematic review of histone lysine-specific demethylase 1 and its inhibitors[J].Med Res Rev,2015,35(5):1032-1071.
[8] LYNCH J T,HARRIS W J,SOMERVAILLE T C.LSD1 inhibition:a therapeutic strategy in cancer?[J].Expert Opin Ther Targets,2012,16(12):1239-1249.
[9] WANG Q,WEI J,SU P,et al.Histone demethylase JARID1C promotes breast cancer metastasis cells via down regulating BRMS1 expression[J].Biochem Biophys Res Commun,2015,464(2):659-666.
[10] LI N,DHAR S S,CHEN T Y,et al.JARID1D is a suppressor and prognostic marker of prostate cancer invasion and metastasis[J].Cancer Res,2016,76(4):831-843.
[11] XU L M,WU W,CHENG G L,et al.Enhancement of proliferation and invasion of gastric cancer cell by KDM5C via decrease in p53 expression[J].Technol Cancer Res Treat,2016,doi:10.1177/1533034616629261
[12] TORRES I O,KUCHENBECKER K M,NNADI C I,et al.Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism[J].Nat Commun,2015,6:6204.
[13] SHEN X,ZHUANG Z,ZHANG Y,et al.JARID1B modulates lung cancer cell proliferation and invasion by regulating p53 expression[J].Tumour Biol,2015,36(9):7133-7142.
[14] TANG B,QI G,TANG F,et al.JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells[J].Oncotarget,2015,6(14):12723-12739.
[15] WANG H,SONG C,DING Y,et al.Transcriptional regulation of JARID1B/KDM5B histone demethylase by ikaros,histone deacetylase 1(HDAC1),and casein kinase 2(CK2) in B-cell acute lymphoblastic leukemia[J].J Biol Chem,2016,291(8):4004-4018.
[16] 卢凯,许斌,陈恕求,等.miR-19a对于去势抵抗性前列腺癌细胞的增殖及凋亡的调控[J].现代医学,2013,41(9):613-616.
[17] AKIMOTO C,KITAGAWA H,MATSUMOTO T,et al.Spermatogenesis-specific association of SMCY and MSH5[J].Genes Cells,2008,13(6):623-633.
[18] KONOVALOV S,GARCIA-BASSETS I.Analysis of the levels of lysine-specific demethylase 1(LSD1) mRNA in human ovarian tumors and the effects of chemical LSD1 inhibitors in ovarian cancer cell lines[J].J Ovarian Res,2013,6(1):75.
[19] SHARMA S V,LEE D Y,LI B,et al.A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations[J].Cell,2010,141(1):69-80.
[20] WANG L,MAO Y,DU G,et al.Overexpression of JARID1B is associated with poor prognosis and chemotherapy resistance in epithelial ovarian cancer[J].Tumour Biol,2015,36(4):2465-2472.
[21] SCHMIDT D M,MCCAFFERTY D G.Trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1[J].Biochemistry,2007,46(14):4408-4416.

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