组蛋白去甲基化酶与肿瘤发生
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摘要
组蛋白甲基化修饰是一个可逆的动态的调节过程。甲基化和/或去甲基化状态与表观遗传、转录调控和维持基因组完整性等密切相关。组蛋白甲基化状态异常会直接或间接影响各种生理和病理过程。已知组蛋白去甲基化酶包括赖氨酸特异性去甲基化酶(LSD)家族和含Jmj C结构域的JMJD家族。研究发现,两者与肿瘤的发生均有着密切的关系。本文总结了组蛋白去甲基化酶在组蛋白甲基化修饰及肿瘤研究方面的最新进展,为组蛋白修饰的功能及肿瘤诊断、治疗、预后监测等研究提供新思路。在胃癌、乳腺癌、结肠癌等常见肿瘤中,组蛋白去甲基化酶可改变组蛋白的甲基化水平或者直接作用于癌基因,也可调节microRNA或转录因子等,促进或抑制肿瘤的发生发展与影响肿瘤的预后。
Histone methylation is a reversible and dynamic process of histone post-translational modification(PTM). Methylation and/or demethylation status of histone are closely related to epigenetic regulation, transcription regulation and maintenance of genome integrity. Histone methylation abnormalities will directly or indirectly affect a variety of physiological and pathological processes.Histone demethylases are known to include the lysine-specific demethylase(LSD) family and the JMJD family of Jmj C-containing domains. Studies have shown that both families are closely related to tumorigenesis. This article summarizes the recent advances of histone demethylases in histone methylation and tumor research,and provides new ideas for the roles of histone modification in tumor diagnosis,treatment and prognosis monitoring. In common tumors such as gastric cancer,breast cancer,and colon cancer,histone demethylases can change the methylation level of histones,directly affect activity of oncogenes,and regulate microRNAs or transcription factors to modulate the occurrence,development and the prognosis of tumors.
Histone methylation is a reversible and dynamic process of histone post-translational modification(PTM). Methylation and/or demethylation status of histone are closely related to epigenetic regulation, transcription regulation and maintenance of genome integrity. Histone methylation abnormalities will directly or indirectly affect a variety of physiological and pathological processes.Histone demethylases are known to include the lysine-specific demethylase(LSD) family and the JMJD family of Jmj C-containing domains. Studies have shown that both families are closely related to tumorigenesis. This article summarizes the recent advances of histone demethylases in histone methylation and tumor research,and provides new ideas for the roles of histone modification in tumor diagnosis,treatment and prognosis monitoring. In common tumors such as gastric cancer,breast cancer,and colon cancer,histone demethylases can change the methylation level of histones,directly affect activity of oncogenes,and regulate microRNAs or transcription factors to modulate the occurrence,development and the prognosis of tumors.
引文
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[2]Greer EL,Shi Y.Histone methylation:a dynamic mark in health,disease and inheritance[J].Nat Rev Genet,2012,13(5):343-357
[3]Nottke A,Colaiácovo MP,Shi Y.Developmental roles of the histone lysine demethylases[J].Development,2009,136(6):879-889
[4]李玮玮,朱莹.组蛋白甲基转移酶SMYD家族与肿瘤[J].中国生物化学与分子生物学报(Li WW,Zhu Y.Histone lysine methyltransferase SMYD family and cancer[J].Chin J Biochem Mol Biol),2018,34(2):142-152
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[7]Tokunaga R,Sakamoto Y,Nakagawa S,et al.The prognostic significance of histone lysine demethylase JMJD3/KDM6B in colorectal cancer[J].Ann Surg Oncol,2016,23(2):678-685
[8]彭晨,覃刚,吴莉莉,等.组蛋白去甲基化酶JMJD3对胃癌细胞增殖凋亡的影响[J].实用医学杂志(Peng C,Tan G,Wu LL,et al.Effect of histone demethylase JMJD3 on proliferation and apoptosis of gastric cancer cells[J].J Pract Med),2017,33(4):517-520
[9]Perrigue PM,Najbauer J,Barciszewski J.Histone demethylase JMJD3 at the intersection of cellular senescence and cancer[J].Biochim Biophys Acta,2016,1865(2):237-244
[10]Yang Y,Zhang YJ,Zhu Y,et al.Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma,nasal-type:a multicenter study[J].Leukemia,2015,29(7):1571-1577
[11]Denis H,Van Grembergen O,Delatte B,et al.MicroRNAs regulate KDM5 histone demethylases in breast cancer cells[J].Mol Biosyst,2016,12(2):404-413
[12]Zhao QY,Lei PJ,Zhang X,et al.Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a four-stage breast cancer model[J].Clin Epigenetics,2016,8(1):34
[13]Liu H,Liu L,Holowatyj A,et al.Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer[J].Mol Carcinog,2016,55(5):977-990
[14]Zhao Z,Sun C,Li F,et al.Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer[J].Int J Clin Exp Pathol,2015,8(9):10325-10334
[15]Hui Z,Yiling C,Wenting Y,et al.miR-491-5p functions as a tumor suppressor by targeting JMJD2B in ERα-positive breast cancer[J].FEBS Lett,2015,589(7):812-821
[16]Shi Y,Lan F,Matson C,et al.Histone demethylation mediated by the nuclear amine oxidase homolog LSD1[J].Cell,2004,119(7):941-953
[17]Tsukada Y,Fang J,Erdjument-Bromage H,et al.Histone demethylation by a family of Jmj C domain-containing proteins[J].Nature,2006,439(7078):811-816
[18]Riveiro AR,Mariani L,Malmberg E,et al.JMJD-1.2/PHF8controls axon guidance by regulating Hedgehog-like signaling[J].Development,2017,144(5):856-865
[19]徐龙勇,陈德桂.组蛋白去甲基化酶研究进展[J].生命科学(Xu LY,Chen DG.Research progress of histone demethylase[J].Chin Bull Life Sci),2010,22(2):109-114
[20]Klose RJ,Kallin EM,Zhang Y.Jmj C-domain-containing proteins and histone demethylation[J].Nat Rev Genet,2006,7(9):715-727
[21]赵丽.JMJD2B在胃癌侵袭转移中的作用研究以及幽门螺杆菌感染对JMJD2B表达调控的研究[D].山东大学(Zhao Li.JMJD2B in the invasion and metastasis of gastric cancer research and Helicobacter pylori infection JMJD2B expression regulation[D].Shandong University),2013
[22]韩凤娟.JMJD2B在幽门螺杆菌介导的胃黏膜上皮细胞恶性转化中的作用研究[D].山东大学(Han Feng-Juan.JMJD2B in Helicobacter pylori-mediated gastric mucosal epithelial cells in the role of malignant transformation[D].Shandong University),2016
[23]王朝阳,李炳辉,郑忠立,等.JMJD1A通过调节c-Myc的表达影响胃癌细胞的增殖及侵袭[J].河南大学学报(医学版)(Wang CY,Li BH,Zhen ZL,et al.JMJD1A affects proliferation and invasion of gastric cancer cells through regulation of c-Myc expression[J].J Henan Univ(Med Sci),2017,36(2):119-122
[24]李晓伟,许冰,刘剑,等.JMJD6在胃癌组织中的表达及意义[J].现代生物医学进展(Li XW,Xu B,Liu J,et al.MJD6expression in gastric cancer and its significance[J].Prog Mod Biomed),2015,15(14):2621-2624
[25]Wolf SS,Patchev VK,Obendorf M.A novel variant of the putative demethylase gene,s-JMJD1C,is a coactivator of the AR[J].Arch Biochem Biophys,2007,460(1):56-66
[26]Shao P,Liu Q,Maina PK,et al.Histone demethylase PHF8promotes epithelial to mesenchymal transition and breast tumorigenesis[J].Nucleic Acids Res,2017,45(4):1687-1702
[27]Wang Q,Ma S,Song N,et al.Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis[J].J Clin Invest,2016,126(6):2205-2220
[28]Wu J,Crowe DL.The histone methyltransferase EZH2 promotes mammary stem and luminal progenitor cell expansion,metastasis and inhibits estrogen receptor-positive cellular differentiation in a model of basal breast cancer[J].Oncol Rep,2015,34(1):455-460
[29]郭晓强,陆菁潇,桂耀庭,等.组蛋白H3K27去甲基化酶与肿瘤发生[J].中国生物化学与分子生物学报(Guo XQ,Lu JX,Gui YT,et al.Histone H3K27 demethylases and tumorigenesis[J].Chin J Biochem Mol Biol),2011,27(8):706-711
[30]Wade MA,Jones D,Wilson L,et al.The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer[J].Nucleic Acids Res,2015,43(1):196-207
[31]Ramadoss S,Guo G,Wang CY.Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53[J].Oncogene,2017,36(1):47-59
[32]Komaragiri SK,Bostanthirige DH,Morton DJ,et al.ID4promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells[J].Biochem Biophys Res Commun,2016,478(1):60-66
[33]Berry WL,Janknecht R.KDM4/JMJD2 histone demethylases:epigenetic regulators in cancer cells[J].Cancer Res,2013,73(10):2936-2942
[34]Suikki HE,Kujala PM,Tammela TL,et al.Genetic alterations and changes in expression of histone demethylases in prostate cancer[J].Prostate,2010,70(8):889-898
[35]Schweizer MT,Yu EY.AR-signaling in human malignancies:prostate cancer and beyond[J].Cancers(Basel),2017,9(1).pii:E 7
[36]Willmann D,Lim S,Wetzel S,et al.Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor[J].Int J Cancer,2012,131(11):2704-2709
[37]Chen ZY,Chen H,Qiu T,et al.Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells[J].Mol Med Rep,2016,14(3):2511-2517
[38]Wang M,Liu X,Jiang G,et al.Relationship between LSD1expression and E-cadherin expression in prostate cancer[J].Int Urol Nephrol,2015,47(3):485-490
[39]Gao S,Chen S,Han D,et al.LSD1 modulates androgen receptor cistrome in prostate cancer via regulation of FOXA1chromatin binding[J].Cancer Res,2017,77(13Supplement):5497-5497
[40]Li J,Wan X,Wu Q,et al.MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation[J].Int J Clin Exp Med,2015,8(4):5329-5339
[41]Han M,Xu W,Cheng P,et al.Histone demethylase lysine demethylase 5B in development and cancer[J].Oncotarget,2017,8(5):8980-8991
[42]Xiang Y,Zhu Z,Han G,et al.JARID1B is a histone H3 lysine4 demethylase up-regulated in prostate cancer[J].Proc Natl Acad Sci U S A,2007,104(49):19226-19231
[43]Li N,Dhar SS,Chen TY,et al.JARID1D is a suppressor and prognostic marker of prostate cancer invasion and metastasis[J].Cancer Res,2016,76(4):831-843
[44]Lu W,Liu S,Li B,et al.SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination[J].Oncotarget,2015,6(2):771-788
[45]Wilson S,Fan L,Sahgal N,et al.The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells[J].Oncotarget,2017,8(18):30328-30343
[46]Lv T,Yuan D,Miao X,et al.Over-expression of LSD1 promotes proliferation,migration and invasion in non-small cell lung cancer[J].PLo S One,2012,7(4):e35065
[47]Ferrari-Amorotti G,Fragliasso V,Esteki R,et al.Inhibiting interactions of lysine demethylase LSD1 with Snail/Slug blocks cancer cell invasion[J].Cancer Res,2013,73(1):235-245
[48]Kauffman EC,Robinson BD,Downes MJ,et al.Role of androgen receptor and associated lysine-demethylase coregulators,LSD1 and JMJD2A,in localized and advanced human bladder cancer[J].Mol Carcinog,2011,50(12):931-944
[49]丁杰,廖国庆,张忠民,等.LSD1、E-钙黏蛋白、N-钙黏蛋白在结肠癌中的表达及其意义[J].中国普通外科杂志(Ding J,Liao GQ,Zhang ZM,et al.Expression of LSD1,E-cadherin and N-cadherin in colon cancer and its significance[J].Chin J Gen Surg),2014,23(4):462-467
[50]骆俊民.JMJD3在结肠癌中的表达及临床意义研究[J].临床医药文献杂志(电子版)(Luo J M.JMJD3 expression in colon cancer and clinical significance[J].J Clin Med Lit(Electr Ed)),2016,3(39):7785-7786
[51]Vangimalla SS,Ganesan M,Kharbanda KK,et al.Bifunctional Enzyme JMJD6 contributes to multiple disease pathogenesis:new twist on the old story[J].Biomolecules,2017,7(2).pii:E41
[52]Lee KH,Park JW,Sung HS,et al.PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer[J].Oncogene,2015,34(22):2897-2909
[2]Greer EL,Shi Y.Histone methylation:a dynamic mark in health,disease and inheritance[J].Nat Rev Genet,2012,13(5):343-357
[3]Nottke A,Colaiácovo MP,Shi Y.Developmental roles of the histone lysine demethylases[J].Development,2009,136(6):879-889
[4]李玮玮,朱莹.组蛋白甲基转移酶SMYD家族与肿瘤[J].中国生物化学与分子生物学报(Li WW,Zhu Y.Histone lysine methyltransferase SMYD family and cancer[J].Chin J Biochem Mol Biol),2018,34(2):142-152
[5]Bhaumik SR,Smith E,Shilatifard A.Covalent modifications of histones during development and disease pathogenesis[J].Nat Struct Mol Biol,2007,14(11):1008-1016
[6]高文龙,刘红林.DOT1——一类新的组蛋白赖氨酸甲基转移酶[J].遗传(Gao WL,Liu HL.DOT1-A new class of histone lysine methyltransferase[J].Hereditas(Beijing)),2007,29(12):1449-1454
[7]Tokunaga R,Sakamoto Y,Nakagawa S,et al.The prognostic significance of histone lysine demethylase JMJD3/KDM6B in colorectal cancer[J].Ann Surg Oncol,2016,23(2):678-685
[8]彭晨,覃刚,吴莉莉,等.组蛋白去甲基化酶JMJD3对胃癌细胞增殖凋亡的影响[J].实用医学杂志(Peng C,Tan G,Wu LL,et al.Effect of histone demethylase JMJD3 on proliferation and apoptosis of gastric cancer cells[J].J Pract Med),2017,33(4):517-520
[9]Perrigue PM,Najbauer J,Barciszewski J.Histone demethylase JMJD3 at the intersection of cellular senescence and cancer[J].Biochim Biophys Acta,2016,1865(2):237-244
[10]Yang Y,Zhang YJ,Zhu Y,et al.Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma,nasal-type:a multicenter study[J].Leukemia,2015,29(7):1571-1577
[11]Denis H,Van Grembergen O,Delatte B,et al.MicroRNAs regulate KDM5 histone demethylases in breast cancer cells[J].Mol Biosyst,2016,12(2):404-413
[12]Zhao QY,Lei PJ,Zhang X,et al.Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a four-stage breast cancer model[J].Clin Epigenetics,2016,8(1):34
[13]Liu H,Liu L,Holowatyj A,et al.Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer[J].Mol Carcinog,2016,55(5):977-990
[14]Zhao Z,Sun C,Li F,et al.Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer[J].Int J Clin Exp Pathol,2015,8(9):10325-10334
[15]Hui Z,Yiling C,Wenting Y,et al.miR-491-5p functions as a tumor suppressor by targeting JMJD2B in ERα-positive breast cancer[J].FEBS Lett,2015,589(7):812-821
[16]Shi Y,Lan F,Matson C,et al.Histone demethylation mediated by the nuclear amine oxidase homolog LSD1[J].Cell,2004,119(7):941-953
[17]Tsukada Y,Fang J,Erdjument-Bromage H,et al.Histone demethylation by a family of Jmj C domain-containing proteins[J].Nature,2006,439(7078):811-816
[18]Riveiro AR,Mariani L,Malmberg E,et al.JMJD-1.2/PHF8controls axon guidance by regulating Hedgehog-like signaling[J].Development,2017,144(5):856-865
[19]徐龙勇,陈德桂.组蛋白去甲基化酶研究进展[J].生命科学(Xu LY,Chen DG.Research progress of histone demethylase[J].Chin Bull Life Sci),2010,22(2):109-114
[20]Klose RJ,Kallin EM,Zhang Y.Jmj C-domain-containing proteins and histone demethylation[J].Nat Rev Genet,2006,7(9):715-727
[21]赵丽.JMJD2B在胃癌侵袭转移中的作用研究以及幽门螺杆菌感染对JMJD2B表达调控的研究[D].山东大学(Zhao Li.JMJD2B in the invasion and metastasis of gastric cancer research and Helicobacter pylori infection JMJD2B expression regulation[D].Shandong University),2013
[22]韩凤娟.JMJD2B在幽门螺杆菌介导的胃黏膜上皮细胞恶性转化中的作用研究[D].山东大学(Han Feng-Juan.JMJD2B in Helicobacter pylori-mediated gastric mucosal epithelial cells in the role of malignant transformation[D].Shandong University),2016
[23]王朝阳,李炳辉,郑忠立,等.JMJD1A通过调节c-Myc的表达影响胃癌细胞的增殖及侵袭[J].河南大学学报(医学版)(Wang CY,Li BH,Zhen ZL,et al.JMJD1A affects proliferation and invasion of gastric cancer cells through regulation of c-Myc expression[J].J Henan Univ(Med Sci),2017,36(2):119-122
[24]李晓伟,许冰,刘剑,等.JMJD6在胃癌组织中的表达及意义[J].现代生物医学进展(Li XW,Xu B,Liu J,et al.MJD6expression in gastric cancer and its significance[J].Prog Mod Biomed),2015,15(14):2621-2624
[25]Wolf SS,Patchev VK,Obendorf M.A novel variant of the putative demethylase gene,s-JMJD1C,is a coactivator of the AR[J].Arch Biochem Biophys,2007,460(1):56-66
[26]Shao P,Liu Q,Maina PK,et al.Histone demethylase PHF8promotes epithelial to mesenchymal transition and breast tumorigenesis[J].Nucleic Acids Res,2017,45(4):1687-1702
[27]Wang Q,Ma S,Song N,et al.Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis[J].J Clin Invest,2016,126(6):2205-2220
[28]Wu J,Crowe DL.The histone methyltransferase EZH2 promotes mammary stem and luminal progenitor cell expansion,metastasis and inhibits estrogen receptor-positive cellular differentiation in a model of basal breast cancer[J].Oncol Rep,2015,34(1):455-460
[29]郭晓强,陆菁潇,桂耀庭,等.组蛋白H3K27去甲基化酶与肿瘤发生[J].中国生物化学与分子生物学报(Guo XQ,Lu JX,Gui YT,et al.Histone H3K27 demethylases and tumorigenesis[J].Chin J Biochem Mol Biol),2011,27(8):706-711
[30]Wade MA,Jones D,Wilson L,et al.The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer[J].Nucleic Acids Res,2015,43(1):196-207
[31]Ramadoss S,Guo G,Wang CY.Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53[J].Oncogene,2017,36(1):47-59
[32]Komaragiri SK,Bostanthirige DH,Morton DJ,et al.ID4promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells[J].Biochem Biophys Res Commun,2016,478(1):60-66
[33]Berry WL,Janknecht R.KDM4/JMJD2 histone demethylases:epigenetic regulators in cancer cells[J].Cancer Res,2013,73(10):2936-2942
[34]Suikki HE,Kujala PM,Tammela TL,et al.Genetic alterations and changes in expression of histone demethylases in prostate cancer[J].Prostate,2010,70(8):889-898
[35]Schweizer MT,Yu EY.AR-signaling in human malignancies:prostate cancer and beyond[J].Cancers(Basel),2017,9(1).pii:E 7
[36]Willmann D,Lim S,Wetzel S,et al.Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor[J].Int J Cancer,2012,131(11):2704-2709
[37]Chen ZY,Chen H,Qiu T,et al.Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells[J].Mol Med Rep,2016,14(3):2511-2517
[38]Wang M,Liu X,Jiang G,et al.Relationship between LSD1expression and E-cadherin expression in prostate cancer[J].Int Urol Nephrol,2015,47(3):485-490
[39]Gao S,Chen S,Han D,et al.LSD1 modulates androgen receptor cistrome in prostate cancer via regulation of FOXA1chromatin binding[J].Cancer Res,2017,77(13Supplement):5497-5497
[40]Li J,Wan X,Wu Q,et al.MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation[J].Int J Clin Exp Med,2015,8(4):5329-5339
[41]Han M,Xu W,Cheng P,et al.Histone demethylase lysine demethylase 5B in development and cancer[J].Oncotarget,2017,8(5):8980-8991
[42]Xiang Y,Zhu Z,Han G,et al.JARID1B is a histone H3 lysine4 demethylase up-regulated in prostate cancer[J].Proc Natl Acad Sci U S A,2007,104(49):19226-19231
[43]Li N,Dhar SS,Chen TY,et al.JARID1D is a suppressor and prognostic marker of prostate cancer invasion and metastasis[J].Cancer Res,2016,76(4):831-843
[44]Lu W,Liu S,Li B,et al.SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination[J].Oncotarget,2015,6(2):771-788
[45]Wilson S,Fan L,Sahgal N,et al.The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells[J].Oncotarget,2017,8(18):30328-30343
[46]Lv T,Yuan D,Miao X,et al.Over-expression of LSD1 promotes proliferation,migration and invasion in non-small cell lung cancer[J].PLo S One,2012,7(4):e35065
[47]Ferrari-Amorotti G,Fragliasso V,Esteki R,et al.Inhibiting interactions of lysine demethylase LSD1 with Snail/Slug blocks cancer cell invasion[J].Cancer Res,2013,73(1):235-245
[48]Kauffman EC,Robinson BD,Downes MJ,et al.Role of androgen receptor and associated lysine-demethylase coregulators,LSD1 and JMJD2A,in localized and advanced human bladder cancer[J].Mol Carcinog,2011,50(12):931-944
[49]丁杰,廖国庆,张忠民,等.LSD1、E-钙黏蛋白、N-钙黏蛋白在结肠癌中的表达及其意义[J].中国普通外科杂志(Ding J,Liao GQ,Zhang ZM,et al.Expression of LSD1,E-cadherin and N-cadherin in colon cancer and its significance[J].Chin J Gen Surg),2014,23(4):462-467
[50]骆俊民.JMJD3在结肠癌中的表达及临床意义研究[J].临床医药文献杂志(电子版)(Luo J M.JMJD3 expression in colon cancer and clinical significance[J].J Clin Med Lit(Electr Ed)),2016,3(39):7785-7786
[51]Vangimalla SS,Ganesan M,Kharbanda KK,et al.Bifunctional Enzyme JMJD6 contributes to multiple disease pathogenesis:new twist on the old story[J].Biomolecules,2017,7(2).pii:E41
[52]Lee KH,Park JW,Sung HS,et al.PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer[J].Oncogene,2015,34(22):2897-2909
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