组蛋白甲基转移酶EZH2基因在三阴性乳腺癌中的研究进展
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摘要
表观遗传学改变是可遗传的改变,并且不引起DNA序列的变化,它与多种肿瘤的发生、发展及预后密切相关。组蛋白甲基化是重要的表观遗传学修饰之一,组蛋白甲基转移酶EZH2基因介导的组蛋白甲基化与三阴性乳腺癌有着密切的关系。BRCA1突变及甲基化是引起三阴性乳腺癌的主要原因之一。EZH2可以与BRCA1相互作用,影响乳腺癌的进展。因此,检测三阴性乳腺癌中EZH2的表达,对于预测患者预后及指导治疗具有重要意义。笔者就组蛋白甲基转移酶EZH2基因与三阴性乳腺癌的关系进行综述。
引文
[1] Kang SP, Martel M, Harris LN. Triple negative breast cancer: current understanding of biology and treatment options [J]. Curr Opin Obstet Gynecol, 2008, 20(1): 40-46.
[2] Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer [J]. J Clin Oncol, 2008, 26(8): 1275-1281.
[3] Sharma S, Kelly TK, Jones PA. Epigenetics in cancer [J]. Carcinogenesis, 2010, 31(1): 27-36.
[4] Schuettengruber B, Chourrout D, Vervoort M, et al. Genome regulation by polycomb and trithorax proteins [J]. Cell, 2007, 128(4): 735-745.
[5] Margueron R, Li G, Sarma K, et al. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms [J]. Mol Cell, 2008, 32(4): 503-518.
[6] Sneeringer CJ, Scott MP, Kuntz KW, et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas [J]. Proc Natl Acad Sci U S A, 2010, 107(49): 20 980-20 985.
[7] Cardoso C, Mignon C, Hetet G, et al. The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders [J]. Eur J Hum Genet, 2000, 8(3): 174-180.
[8] Di Croce L, Helin K. Transcriptional regulation by polycomb group proteins [J]. Nat Struct Mol Biol, 2013, 20(10): 1147-1155.
[9] Sauvageau M, Sauvageau G. Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer [J]. Cell Stem Cell, 2010, 7(3): 299-313.
[10] Francis NJ, Kingston RE, Woodcock CL. Chromatin compaction by a polycomb group protein complex [J]. Science, 2004, 306(5701): 1574-1577.
[11] Zhou W, Zhu P, Wang J, et al. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase Ⅱ transcriptional elongation [J]. Mol Cell, 2008, 29(1): 69-80.
[12] Liu C, Li S, Dai X, et al. PRC2 regulates RNA polymerase Ⅲ transcribed non-translated RNA gene transcription through EZH2 and SUZ12 interaction with TFⅢC complex [J]. Nucleic Acids Res, 2015, 43(13): 6270-6284.
[13] Guo S, Li X, Rohr J, et al. EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features [J]. Diagn Pathol, 2016, 11: 41.
[14] Jang SH, Lee JE, Oh MH, et al. High EZH2 protein expression is associated with poor overall survival in patients with luminal A breast cancer [J]. J Breast Cancer, 2016, 19(1): 53-60.
[15] Ko HW, Lee HH, Huo L, et al. GSK3beta inactivation promotes the oncogenic functions of EZH2 and enhances methylation of H3K27 in human breast cancers [J]. Oncotarget, 2016, 7(35):57 131-57 144.
[16] Mahara S, Lee PL, Feng M, et al. HIFI-alpha activation underlies a functional switch in the paradoxical role of Ezh2/PRC2 in breast cancer [J]. Proc Natl Acad Sci U S A, 2016, 113(26): E3735-3744.
[17] Yang CC, LaBaff A, Wei Y, et al. Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers [J]. Am J Transl Res, 2015, 7(6): 1009-1020.
[18] Tao R, Chen Z, Wu P, et al. The possible role of EZH2 and DNMT1 polymorphisms in sporadic triple-negative breast carcinoma in southern Chinese females [J]. Tumour Biol, 2015, 36(12): 9849-9855.
[19] Lips EH, Mulder L, Oonk A, et al. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers [J]. Br J Cancer, 2013, 108(10): 2172-2177.
[20] Carey L, Winer E, Viale G, et al. Triple-negative breast cancer: disease entity or title of convenience? [J]. Nat Rev Clin Oncol, 2010, 7(12): 683-692.
[21] Gonzalez-Angulo AM, Timms KM, Liu S, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer [J]. Clin Cancer Res, 2011, 17(5): 1082-1089.
[22] Jung J, Kang E, Gwak JM, et al. Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients [J]. Curr Oncol, 2016, 23(5): 298-303.
[23] Rashid MU, Muhammad N, Bajwa S, et al. High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients [J]. BMC Cancer, 2016, 16(1): 673.
[24] Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer [J]. Oncogene, 2007, 26(14): 2126-2132.
[25] Yamashita N, Tokunaga E, Kitao H, et al. Epigenetic inactivation of BRCA1 through promoter hypermethylation and its clinical importance in triple-negative breast cancer [J]. Clin Breast Cancer, 2015, 15(6): 498-504.
[26] Stefansson OA, Jonasson JG, Olafsdottir K, et al. CpG island hypermethylation of BRCA1 and loss of pRb as co-occurring events in basal/triple-negative breast cancer [J]. Epigenetics, 2011, 6(5): 638-649.
[27] Kim MC, Choi JE, Lee SJ, et al. Coexistent loss of the expressions of BRCA1 and p53 predicts poor prognosis in triple-negative breast cancer [J]. Ann Surg Oncol, 2016(11), 23: 3524-3530.
[28] Gong C, Fujino K, Monteiro LJ, et al. FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer [J]. Oncogene, 2015, 34(39): 5012-5024.
[29] Gong C, Yao S, Gomes AR, et al. BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer [J]. Oncogenesis, 2016, 5: e214.
[30] Wang L, Zeng X, Chen S, et al. BRCA1 is a negative modulator of the PRC2 complex [J]. EMBO J, 2013, 32(11): 1584-1597.
[31] Gonzalez ME, DuPrie ML, Krueger H, et al. Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer [J]. Cancer Res, 2011, 71(6): 2360-2370.
[32] Gonzalez ME, Li X, Toy K, et al. Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1 [J]. Oncogene, 2009, 28(6): 843-853.
[33] Rajabi H, Hiraki M, Tagde A, et al. MUC1-C activates EZH2 expression and function in human cancer cells [J]. Sci Rep, 2017, 7(1): 7481.
[34] Xiao L, Tien JC, Vo J, et al. Epigenetic reprogramming with antisense oligonucleotides enhances the effectiveness of androgen receptor inhibition in castration-resistant prostate cancer [EB/OL]. [2018-08-22].http://cancerres.aacrjournals.org/content/early/2018/08/22/0008-5472.CAN-18-0941.long.
[35] Anwar T, Arellano-Garcia C, Ropa J, et al. p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis [J]. Nat Commun, 2018, 9(1): 2801.
[36] Karakashev S, Zhu H, Wu S, et al. CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [J]. Nat Commun, 2018, 9(1): 631.
[37] Puppe J, Drost R, Liu X, et al. BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to polycomb repressive complex 2-inhibitor 3-deazaneplanocin A [J]. Breast Cancer Res, 2009, 11(4): R63.
[38] Fan T, Jiang S, Chung N, et al. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression [J]. Mol Cancer Res, 2011, 9(4): 418-429.
[39] Richon VM, Johnston D, Sneeringer CJ, et al. Chemogenetic analysis of human protein methyltransferases [J]. Chem Biol Drug Des, 2011, 78(2): 199-210.
[40] Miranda TB, Cortez CC, Yoo CB, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation [J]. Mol Cancer Ther, 2009, 8(6): 1579-1588.
[41] Knutson SK, Wigle TJ, Warholic NM, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells [J]. Nat Chem Biol, 2012, 8(11): 890-896.
[42] Knutson SK, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma [J]. Mol Cancer Ther, 2014, 13(4): 842-854.
[43] Qi W, Chan H, Teng L, et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation [J]. Proc Natl Acad Sci U S A, 2012, 109(52): 21 360-21 365.
[44] Konze KD, Ma A, Li F, et al. An orally bioavailable chemical probe of the lysine methyltransferases EZH2 and EZH1 [J]. ACS Chem Biol, 2013, 8(6): 1324-1334.
[45] McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations [J]. Nature, 2012, 492(7427): 108-112.
[46] Song X, Gao T, Wang N, et al. Corrigendum: selective inhibition of EZH2 by ZLD1039 blocks H3K27methylation and leads to potent anti-tumor activity in breast cancer [J]. Sci Rep, 2016, 6: 24893.
[47] Dimri M, Bommi PV, Sahasrabuddhe AA, et al. Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells [J]. Carcinogenesis, 2010, 31(3): 489-495.
[48] Hua WF, Fu YS, Liao YJ, et al. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells [J]. Eur J Pharmacol, 2010, 637(1-3): 16-21.
[2] Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer [J]. J Clin Oncol, 2008, 26(8): 1275-1281.
[3] Sharma S, Kelly TK, Jones PA. Epigenetics in cancer [J]. Carcinogenesis, 2010, 31(1): 27-36.
[4] Schuettengruber B, Chourrout D, Vervoort M, et al. Genome regulation by polycomb and trithorax proteins [J]. Cell, 2007, 128(4): 735-745.
[5] Margueron R, Li G, Sarma K, et al. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms [J]. Mol Cell, 2008, 32(4): 503-518.
[6] Sneeringer CJ, Scott MP, Kuntz KW, et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas [J]. Proc Natl Acad Sci U S A, 2010, 107(49): 20 980-20 985.
[7] Cardoso C, Mignon C, Hetet G, et al. The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders [J]. Eur J Hum Genet, 2000, 8(3): 174-180.
[8] Di Croce L, Helin K. Transcriptional regulation by polycomb group proteins [J]. Nat Struct Mol Biol, 2013, 20(10): 1147-1155.
[9] Sauvageau M, Sauvageau G. Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer [J]. Cell Stem Cell, 2010, 7(3): 299-313.
[10] Francis NJ, Kingston RE, Woodcock CL. Chromatin compaction by a polycomb group protein complex [J]. Science, 2004, 306(5701): 1574-1577.
[11] Zhou W, Zhu P, Wang J, et al. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase Ⅱ transcriptional elongation [J]. Mol Cell, 2008, 29(1): 69-80.
[12] Liu C, Li S, Dai X, et al. PRC2 regulates RNA polymerase Ⅲ transcribed non-translated RNA gene transcription through EZH2 and SUZ12 interaction with TFⅢC complex [J]. Nucleic Acids Res, 2015, 43(13): 6270-6284.
[13] Guo S, Li X, Rohr J, et al. EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features [J]. Diagn Pathol, 2016, 11: 41.
[14] Jang SH, Lee JE, Oh MH, et al. High EZH2 protein expression is associated with poor overall survival in patients with luminal A breast cancer [J]. J Breast Cancer, 2016, 19(1): 53-60.
[15] Ko HW, Lee HH, Huo L, et al. GSK3beta inactivation promotes the oncogenic functions of EZH2 and enhances methylation of H3K27 in human breast cancers [J]. Oncotarget, 2016, 7(35):57 131-57 144.
[16] Mahara S, Lee PL, Feng M, et al. HIFI-alpha activation underlies a functional switch in the paradoxical role of Ezh2/PRC2 in breast cancer [J]. Proc Natl Acad Sci U S A, 2016, 113(26): E3735-3744.
[17] Yang CC, LaBaff A, Wei Y, et al. Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers [J]. Am J Transl Res, 2015, 7(6): 1009-1020.
[18] Tao R, Chen Z, Wu P, et al. The possible role of EZH2 and DNMT1 polymorphisms in sporadic triple-negative breast carcinoma in southern Chinese females [J]. Tumour Biol, 2015, 36(12): 9849-9855.
[19] Lips EH, Mulder L, Oonk A, et al. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers [J]. Br J Cancer, 2013, 108(10): 2172-2177.
[20] Carey L, Winer E, Viale G, et al. Triple-negative breast cancer: disease entity or title of convenience? [J]. Nat Rev Clin Oncol, 2010, 7(12): 683-692.
[21] Gonzalez-Angulo AM, Timms KM, Liu S, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer [J]. Clin Cancer Res, 2011, 17(5): 1082-1089.
[22] Jung J, Kang E, Gwak JM, et al. Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients [J]. Curr Oncol, 2016, 23(5): 298-303.
[23] Rashid MU, Muhammad N, Bajwa S, et al. High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients [J]. BMC Cancer, 2016, 16(1): 673.
[24] Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer [J]. Oncogene, 2007, 26(14): 2126-2132.
[25] Yamashita N, Tokunaga E, Kitao H, et al. Epigenetic inactivation of BRCA1 through promoter hypermethylation and its clinical importance in triple-negative breast cancer [J]. Clin Breast Cancer, 2015, 15(6): 498-504.
[26] Stefansson OA, Jonasson JG, Olafsdottir K, et al. CpG island hypermethylation of BRCA1 and loss of pRb as co-occurring events in basal/triple-negative breast cancer [J]. Epigenetics, 2011, 6(5): 638-649.
[27] Kim MC, Choi JE, Lee SJ, et al. Coexistent loss of the expressions of BRCA1 and p53 predicts poor prognosis in triple-negative breast cancer [J]. Ann Surg Oncol, 2016(11), 23: 3524-3530.
[28] Gong C, Fujino K, Monteiro LJ, et al. FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer [J]. Oncogene, 2015, 34(39): 5012-5024.
[29] Gong C, Yao S, Gomes AR, et al. BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer [J]. Oncogenesis, 2016, 5: e214.
[30] Wang L, Zeng X, Chen S, et al. BRCA1 is a negative modulator of the PRC2 complex [J]. EMBO J, 2013, 32(11): 1584-1597.
[31] Gonzalez ME, DuPrie ML, Krueger H, et al. Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer [J]. Cancer Res, 2011, 71(6): 2360-2370.
[32] Gonzalez ME, Li X, Toy K, et al. Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1 [J]. Oncogene, 2009, 28(6): 843-853.
[33] Rajabi H, Hiraki M, Tagde A, et al. MUC1-C activates EZH2 expression and function in human cancer cells [J]. Sci Rep, 2017, 7(1): 7481.
[34] Xiao L, Tien JC, Vo J, et al. Epigenetic reprogramming with antisense oligonucleotides enhances the effectiveness of androgen receptor inhibition in castration-resistant prostate cancer [EB/OL]. [2018-08-22].http://cancerres.aacrjournals.org/content/early/2018/08/22/0008-5472.CAN-18-0941.long.
[35] Anwar T, Arellano-Garcia C, Ropa J, et al. p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis [J]. Nat Commun, 2018, 9(1): 2801.
[36] Karakashev S, Zhu H, Wu S, et al. CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [J]. Nat Commun, 2018, 9(1): 631.
[37] Puppe J, Drost R, Liu X, et al. BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to polycomb repressive complex 2-inhibitor 3-deazaneplanocin A [J]. Breast Cancer Res, 2009, 11(4): R63.
[38] Fan T, Jiang S, Chung N, et al. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression [J]. Mol Cancer Res, 2011, 9(4): 418-429.
[39] Richon VM, Johnston D, Sneeringer CJ, et al. Chemogenetic analysis of human protein methyltransferases [J]. Chem Biol Drug Des, 2011, 78(2): 199-210.
[40] Miranda TB, Cortez CC, Yoo CB, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation [J]. Mol Cancer Ther, 2009, 8(6): 1579-1588.
[41] Knutson SK, Wigle TJ, Warholic NM, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells [J]. Nat Chem Biol, 2012, 8(11): 890-896.
[42] Knutson SK, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma [J]. Mol Cancer Ther, 2014, 13(4): 842-854.
[43] Qi W, Chan H, Teng L, et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation [J]. Proc Natl Acad Sci U S A, 2012, 109(52): 21 360-21 365.
[44] Konze KD, Ma A, Li F, et al. An orally bioavailable chemical probe of the lysine methyltransferases EZH2 and EZH1 [J]. ACS Chem Biol, 2013, 8(6): 1324-1334.
[45] McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations [J]. Nature, 2012, 492(7427): 108-112.
[46] Song X, Gao T, Wang N, et al. Corrigendum: selective inhibition of EZH2 by ZLD1039 blocks H3K27methylation and leads to potent anti-tumor activity in breast cancer [J]. Sci Rep, 2016, 6: 24893.
[47] Dimri M, Bommi PV, Sahasrabuddhe AA, et al. Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells [J]. Carcinogenesis, 2010, 31(3): 489-495.
[48] Hua WF, Fu YS, Liao YJ, et al. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells [J]. Eur J Pharmacol, 2010, 637(1-3): 16-21.