Skip to main content

Advertisement

SpringerLink
Log in

Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Uterine fibroids (UFs) are benign smooth muscle neoplasms affecting up to 70% of reproductive age women. Treatment of symptomatic UFs places a significant economic burden on the US health-care system. Several specific genetic abnormalities have been described as etiologic factors of UFs, suggesting that a low DNA damage repair capacity may be involved in the formation of UF. In this study, we used human fibroid and adjacent myometrial tissues, as well as an in vitro cell culture model, to evaluate the expression of MutS homolog 2 (MSH2), which encodes a protein belongs to the mismatch repair system. In addition, we deciphered the mechanism by which polycomb repressive complex 2 protein, EZH2, deregulates MSH2 in UFs. The RNA expression analysis demonstrated the deregulation of MSH2 expression in UF tissues in comparison to its adjacent myometrium. Notably, protein levels of MSH2 were upregulated in 90% of fibroid tissues (9 of 10) as compared to matched adjacent myometrial tissues. Human fibroid primary cells treated with 3-deazaneplanocin A (DZNep), chemical inhibitor of EZH2, exhibited a significant increase in MSH2 expression (P <.05). Overexpression of EZH2 using an adenoviral vector approach significantly downregulated the expression of MSH2 (P <.05). Chromatin immunoprecipitation assay demonstrated that enrichment of H3K27me3 in promoter regions of MSH2 was significantly decreased in DZNep-treated fibroid cells as compared to vehicle control. These data suggest that EZH2-H3K27me3 regulatory mechanism dynamically changes the expression levels of DNA mismatch repair gene MSH2, through epigenetic mark H3K27me3. MSH2 may be considered as a marker for early detection of UFs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bulun, SE Uterine fibroids. N Engl J Med. 2013;369(14): 1344–1355.

    CAS  PubMed  Google Scholar 

  2. Al-Hendy, A, Salama, S Gene therapy and uterine leiomyoma: a review. Hum Reprod Update. 2006;12(4):385–400.

    CAS  PubMed  Google Scholar 

  3. Heinonen, HR, Sarvilinna, NS, Sjoberg, J, et al. MED12 mutation frequency in unselected sporadic uterine leiomyomas. Fertil Steril. 2014;102(4):1137–1142.

    CAS  PubMed  Google Scholar 

  4. Rieker, RJ, Agaimy, A, Moskalev, EA, et al. Mutation status of the mediator complex subunit 12 (MED12) in uterine leiomyomas and concurrent/metachronous multifocal peritoneal smooth muscle nodules (leiomyomatosis peritonealis disseminata). Pathology. 2013;45(4):388–392.

    CAS  PubMed  Google Scholar 

  5. Halder, SK, Laknaur, A, Miller, J, Layman, LC, Diamond, M, Al- Hendy, A Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids. Mol Genet Genomics. 2015;290(2):505–511.

    CAS  PubMed  Google Scholar 

  6. Bertsch, E, Qiang, W, Zhang, Q, et al. MED12 and HMGA2 muta-tions: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod Pathol. 2014;27(8):1144–1153.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Hunter, DS, Klotzbucher, M, Kugoh, H, et al. Aberrant expression of HMGA2 in uterine leiomyoma associated with loss of TSC2 tumor suppressor gene function. Cancer Res. 2002;62(13): 3766–3772.

    CAS  PubMed  Google Scholar 

  8. Ingraham, SE, Lynch, RA, Surti, U, et al. Identification and char-acterization of novel human transcripts embedded within HMGA2 in t(12;14)(q15;q24.1) uterine leiomyoma. Mutat Res. 2006;602(1-2):43–53.

    CAS  PubMed  Google Scholar 

  9. El-Shennawy, GA, Elbialy, AA, Isamil, AE, El Behery, MM Is genetic polymorphism of ER-alpha, CYP1A1, and CYP1B1 a risk factor for uterine leiomyoma? Arch Gynecol Obstet. 2011;283(6): 1313–1318.

    PubMed  Google Scholar 

  10. Vikhliaeva, EM Molecular-genetic determinants of the neo-plastic process and state-of-the-art treatment of patients with uterine leiomyoma [in Russian]. Vopr Onkol. 2001;47(2): 200–204.

    CAS  PubMed  Google Scholar 

  11. Yang, Y, Zhai, XD, Gao, LB, Li, SL, Wang, Z, Chen, GD Genetic polymorphisms of DNA repair gene XRCC1 and risk of uterine leiomyoma. Mol Cell Biochem. 2010;338(1-2):143–147.

    CAS  PubMed  Google Scholar 

  12. Ramos, JM, Ruiz, A, Colen, R, Lopez, ID, Grossman, L, Matta, JL DNA repair and breast carcinoma susceptibility in women. Can-cer. 2004;100(7):1352–1357.

    CAS  Google Scholar 

  13. Ricks-Santi, LJ, Sucheston, LE, Yang, Y, et al. Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk. BMC Cancer. 2011; 11:278.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Helleday, T, Petermann, E, Lundin, C, Hodgson, B, Sharma, RA DNA repair pathways as targets for cancer therapy. Nat Rev Can-cer. 2008;8(3):193–204.

    CAS  Google Scholar 

  15. Benhamou, S, Sarasin, A Variability in nucleotide excision repair and cancer risk: a review. Mutat Res. 2000;462(2-3): 149–158.

    CAS  PubMed  Google Scholar 

  16. Matta, JL, Villa, JL, Ramos, JM, et al. DNA repair and nonmela-noma skin cancer in Puerto Rican populations. J Am Acad Der-matol. 2003;49(3):433–439.

    Google Scholar 

  17. Belcheva, A, Kolaj, B, Martin, A Missing mismatch repair: a key to T cell immortality. Leuk Lymphoma. 2010;51(10): 1777–1778.

    PubMed  Google Scholar 

  18. Vilar, E, Gruber, SB Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol. 2010;7(3): 153–162.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bachmann, IM, Halvorsen, OJ, Collett, K, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor sub-groups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol. 2006;24(2):268–273.

    CAS  PubMed  Google Scholar 

  20. Kleer, CG, Cao, Q, Varambally, S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003;100(20): 11606–11611.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee, W, Teckie, S, Wiesner, T, et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet. 2014;46(11):1227–1232.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Majewski, IJ, Blewitt, ME, de Graaf, CA, et al. Polycomb repres-sive complex 2 (PRC2) restricts hematopoietic stem cell activity. PLoS Biol. 2008;6(4):e93.

    PubMed  PubMed Central  Google Scholar 

  23. Stefansson, OA, Esteller, M EZH2-mediated epigenetic repression of DNA repair in promoting breast tumor initiating cells. Breast Cancer Res. 2011;13(3):309.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Yoo, KH, Hennighausen, L EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci. 2012; 8(1):59–65.

    CAS  PubMed  Google Scholar 

  25. Yu, H, Simons, DL, Segall, I, et al. PRC2/EED-EZH2 complex is up-regulated in breast cancer lymph node metastasis compared to primary tumor and correlates with tumor proliferation in situ. PloS One. 2012;7(12):e51239.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Yamaguchi, H, Hung, MC Regulation and role of EZH2 in cancer. Cancer Res Treat. 2014;46(3):209–222.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Chang, CJ, Hung, MC The role of EZH2 in tumour progression. Br J Cancer. 2012;106(2):243–247.

    CAS  PubMed  Google Scholar 

  28. Chen, YH, Hung, MC, Li, LY EZH2: a pivotal regulator in con-trolling cell differentiation. Am J Transl Res. 2012;4(4): 364–375.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Holm, K, Grabau, D, Lovgren, K, et al. Global H3K27 trimethyla-tion and EZH2 abundance in breast tumor subtypes. Mol Oncol. 2012;6(5):494–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Tan, JZ, Yan, Y, Wang, XX, Jiang, Y, Xu, HE EZH2: biology, disease, and structure-based drug discovery. Acta Pharmacol Sin. 2014;35(2):161–174.

    CAS  PubMed  Google Scholar 

  31. Kondo, Y Targeting histone methyltransferase EZH2 as cancer treatment. J Biochem. 2014;156(5):249–257.

    CAS  PubMed  Google Scholar 

  32. Chang, CJ, Yang, JY, Xia, W, et al. EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling. Cancer Cell. 2011;19(1):86–100.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Puppe, J, Drost, R, Liu, X, et al. BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to poly-comb repressive complex 2-inhibitor 3-deazaneplanocin. A Breast Cancer Res. 2009;11(4):R63.

    PubMed  Google Scholar 

  34. Zeidler, M, Varambally, S, Cao, Q, et al. The polycomb group protein EZH2 impairs DNA repair in breast epithelial cells. Neo-plasia. 2005;7(11):1011–1019.

    CAS  Google Scholar 

  35. Akinyemi, BO, Adewoye, BR, Fakoya, TA Uterine fibroid: a review. Niger J Med. 2004;13(4):318–329.

    CAS  PubMed  Google Scholar 

  36. Yang, Q, Mas, A, Diamond, MP, Al-Hendy, A The mechanism and function of epigenetics in uterine leiomyoma development. Reprod Sci. 2016;23(2):163–175.

    CAS  PubMed  Google Scholar 

  37. Carney, SA, Tahara, H, Swartz, CD, et al. Immortalization of human uterine leiomyoma and myometrial cell lines after induction of telomerase activity: molecular and phenotypic characteristics. Lab Invest. 2002;82(6):719–728.

    CAS  PubMed  Google Scholar 

  38. Halder, SK, Osteen, KG, Al-Hendy, A Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod. 2013;28(9): 2407–2416.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Nair, S, Curiel, DT, Rajaratnam, V, Thota, C, Al-Hendy, A Target-ing adenoviral vectors for enhanced gene therapy of uterine leio-myomas. Hum Reprod. 2013;28(9):2398–2406.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Nair, S, Saed, GM, Atta, HM, et al. Towards gene therapy of post-operative adhesions: fiber and transcriptional modifications enhance adenovirus targeting towards human adhesion cells. Gynecol Obstet Invest. 2013;76(2):119–124.

    CAS  PubMed  Google Scholar 

  41. Yang, Q, Sun, M, Ramchandran, R, Raj, JU IGF-1 signaling in neonatal hypoxia-induced pulmonary hypertension: role of epige-netic regulation. Vascular Pharmacol. 2015;73:20–31.

    CAS  Google Scholar 

  42. Yang, Q, Tian, Y, Ostler, KR, et al. Epigenetic alterations differ in phenotypically distinct human neuroblastoma cell lines. BMC Cancer. 2010;10:286.

    PubMed  PubMed Central  Google Scholar 

  43. Yang, Q, Dahl, MJ, Albertine, KH, Ramchandran, R, Sun, M, Raj, JU Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells. Cell Prolif. 2013;46(6):654–664.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Iwahashi, Y, Ito, E, Yanagisawa, Y, et al. Promoter analysis of the human mismatch repair gene hMSH2. Gene. 1998;213(1-2): 141–147.

    CAS  PubMed  Google Scholar 

  45. Yamamoto, H, Imai, K Microsatellite instability: an update. Arch Toxicol. 2015;89(6):899–921.

    CAS  PubMed  Google Scholar 

  46. Campbell, MR, Wang, Y, Andrew, SE, Liu, Y MsH2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect. Oncogene. 2006;25(17):2531–2536.

    CAS  PubMed  Google Scholar 

  47. Campbell, MR, Nation, PN, Andrew, SE A lack of DNA mismatch repair on an athymic murine background predisposes to hemato-logic malignancy. Cancer Res. 2005;65(7):2626–2635.

    CAS  PubMed  Google Scholar 

  48. Wheeler, VC, Lebel, LA, Vrbanac, V, Teed, A, te Riele, H, MacDonald, ME Mismatch repair gene MsH2 modifies the timing of early disease in Hdh(Q111) striatum. Hum Mol Genet. 2003;12(3):273–281.

    CAS  PubMed  Google Scholar 

  49. Lal, G, Ash, C, Hay, K, et al. Suppression of intestinal polyps in MsH2-deficient and non-MsH2-deficient multiple intestinal neo-plasia mice by a specific cyclooxygenase-2 inhibitor and by a dual cyclooxygenase-1/2 inhibitor. Cancer Res. 2001;61(16): 6131–6136.

    CAS  PubMed  Google Scholar 

  50. Bridge, G, Rashid, S, Martin, SA DNA mismatch repair and oxi-dative DNA damage: implications for cancer biology and treatment. Cancers. 2014;6(3):1597–1614.

    PubMed  PubMed Central  Google Scholar 

  51. Russo, MT, De Luca, G, Casorelli, I, et al. Role of MUTYH and MSH2 in the control of oxidative DNA damage, genetic instability, and tumorigenesis. Cancer Res. 2009;69(10): 4372–4379.

    CAS  PubMed  Google Scholar 

  52. Meira, LB, Cheo, DL, Reis, AM, et al. Mice defective in the mismatch repair gene MsH2 show increased predisposition to UVB radiation-induced skin cancer. DNA Repair. 2002;1(11): 929–934.

    CAS  PubMed  Google Scholar 

  53. Reitmair, AH, Schmits, R, Ewel, A, et al. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet. 1995; 11(1):64–70.

    CAS  PubMed  Google Scholar 

  54. Yoo, KH, Won, KY, Lim, SJ, Park, YK, Chang, SG Deficiency of MSH2 expression is associated with clear cell renal cell carci-noma. Oncol Lett. 2014;8(5):2135–2139.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Pritchard, CC, Morrissey, C, Kumar, A, et al. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat Commun. 2014;5:4988.

    CAS  PubMed  Google Scholar 

  56. Haraldsdottir, S, Hampel, H, Tomsic, J, et al. Colon and endome-trial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology. 2014;147(6):1308–1316.e1301.

    PubMed  Google Scholar 

  57. Amant, F, Dorfling, CM, Dreyer, L, Vergote, I, Lindeque, BG, Van Rensburg, EJ Microsatellite instability in uterine sarcomas. Int J Gynecol Cancer. 2001;11(3):218–223.

    CAS  PubMed  Google Scholar 

  58. Hoang, LN, Ali, RH, Lau, S, Gilks, CB, Lee, CH Immunohisto-chemical survey of mismatch repair protein expression in uterine sarcomas and carcinosarcomas. Int J Gynecol Pathol. 2014;33(5): 483–491.

    CAS  PubMed  Google Scholar 

  59. Varambally, S, Dhanasekaran, SM, Zhou, M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–629.

    CAS  PubMed  Google Scholar 

  60. Visser, HP, Gunster, MJ, Kluin-Nelemans, HC, et al. The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma. Br J Haematol. 2001;112(4): 950–958.

    CAS  PubMed  Google Scholar 

  61. Cao, W, Younis, RH, Li, J, et al. EZH2 promotes malignant phe-notypes and is a predictor of oral cancer development in patients with oral leukoplakia. Cancer Prev Res (Phila). 2011;4(11): 1816–1824.

    CAS  Google Scholar 

  62. Chase, A, Cross, NC Aberrations of EZH2 in cancer. Clin Cancer Res. 2011;17(9):2613–2618.

    CAS  PubMed  Google Scholar 

  63. Simon, JA, Lange, CA Roles of the EZH2 histone methyl-transferase in cancer epigenetics. Mutat Res. 2008;647(1-2): 21–29.

    CAS  PubMed  Google Scholar 

  64. Wu, Z, Lee, ST, Qiao, Y, et al. Polycomb protein EZH2 regulates cancer cell fate decision in response to DNA damage. Cell Death Differ. 2011;18(11):1771–1779.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Sauvageau, M, Sauvageau, G Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell. 2010;7(3):299–313.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Nakagawa, S, Sakamoto, Y, Okabe, H, et al. Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A inhibits the growth of cholangiocarcinoma cells. Oncol Rep. 2014;31(2):983–988.

    CAS  PubMed  Google Scholar 

  67. Kikuchi, J, Takashina, T, Kinoshita, I, et al. Epigenetic therapy with 3-deazaneplanocin, A, an inhibitor of the histone methyltransfer-ase EZH2, inhibits growth of non-small cell lung cancer cells. Lung Cancer. 2012;78(2):138–143.

    PubMed  Google Scholar 

  68. Crea, F, Hurt, EM, Mathews, LA, et al. Pharmacologic disruption of polycomb repressive complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Mol Cancer. 2011; 10:40.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Kondo, Y, Shen, L, Cheng, AS, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet. 2008;40(6):741–750.

    CAS  PubMed  Google Scholar 

  70. Bracken, AP, Kleine-Kohlbrecher, D, Dietrich, N, et al. The poly-comb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21(5): 525–530.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 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. Mol Cancer Res. 2011; 9(4):418–429.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Zhong, J, Min, L, Huang, H, et al. EZH2 regulates the expression of p16 in the nasopharyngeal cancer cells. Technol Cancer Res Treat. 2013;12(3):269–274.

    CAS  PubMed  Google Scholar 

  73. Lin, L, Zheng, Y, Tu, Y, et al. MicroRNA-144 suppresses tumor-igenesis and tumor progression of astrocytoma by targeting EZH2. Hum Pathol. 2015;46(7):971–980.

    CAS  PubMed  Google Scholar 

  74. Chen, DL, Zhang, DS, Lu, YX, et al. microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer. Oncotarget. 2015;6(13): 10868–10879.

    PubMed  PubMed Central  Google Scholar 

  75. Liu, F, He, Y, Shu, R, Wang, S MicroRNA-1297 regulates hepato-cellular carcinoma cell proliferation and apoptosis by targeting EZH2. Int J Clin Exp Pathol. 2015;8(5):4972–4980.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Sun, J, Zheng, G, Gu, Z, Guo, Z MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2. J Neurooncol. 2015;122(3):481–489.

    CAS  PubMed  Google Scholar 

  77. Canevari, RA, Pontes, A, Rosa, FE, Rainho, CA, Rogatto, SR Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis. Am J Obstet Gynecol. 2005;193(4): 1395–1403.

    PubMed  Google Scholar 

  78. French, D, Cermele, C, Lombardi, AM, et al. Microsatellite altera-tions in uterine leiomyomas. Anticancer Res. 1998;18(1A): 349–351.

    CAS  PubMed  Google Scholar 

  79. Li, M, Liu, L, Wang, Z, et al. Overexpression of hMSH2 and hMLH1 protein in certain gastric cancers and their surrounding mucosae. Oncol Rep. 2008;19(2):401–406.

    PubMed  Google Scholar 

  80. Dracea, A, Angelescu, C, Danciulescu, M, Ciurea, M, Ioana, M, Burada, F Mismatch repair gene expression in gastroesophageal cancers. Turk J Gastroenterol. 2015;26(5):373–377.

    PubMed  Google Scholar 

  81. Zhang, M, Xiang, S, Joo, HY, et al. HDAC6 deacetylates and ubi-quitinates MSH2 to maintain proper levels of MutSa. Molecular Cell. 2014;55(1):31–46.

    PubMed  PubMed Central  Google Scholar 

  82. Tan, J, Yang, X, Zhuang, L, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selec-tively induces apoptosis in cancer cells. Genes Dev. 2007;21(9): 1050–1063.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Muller, J, Verrijzer, P Biochemical mechanisms of gene regulation by polycomb group protein complexes. Curr Opin Genet Dev. 2009;19(2):150–158.

    PubMed  Google Scholar 

  84. Volkel, P, Dupret, B, Le Bourhis, X, Angrand, PO Diverse involvement of EZH2 in cancer epigenetics. Am J Transl Res. 2015;7(2): 175–193.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Shi, B, Liang, J, Yang, X, et al. Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells. Mol Cell Biol. 2007;27(14):5105–5119.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Lee, ST, Li, Z, Wu, Z, et al. Context-specific regulation of NF-kappaB target gene expression by EZH2 in breast cancers. Molecular Cell. 2011;43(5):798–810.

    CAS  PubMed  Google Scholar 

  87. Gao, SB, Zheng, QF, Xu, B, et al. EZH2 represses target genes through H3K27-dependent and H3K27-independent mechanisms in hepatocellular carcinoma. Mol Cancer Res. 2014;12(10): 1388–1397.

    CAS  PubMed  Google Scholar 

  88. Zeidler, M, Kleer, CG The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer. J Mol Histol. 2006;37(5-7):219–223.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Translational Research, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, 1120 15th street, CB2210, Augusta, GA, 30912, USA

    Qiwei Yang PhD, Archana Laknaur MS, Lelyand Elam BS, Larisa Gavrilova-Jordan MD, John Lue MD, Michael P. Diamond MD & Ayman Al-Hendy MD, PhD

  2. Clinical Microbiology Division, Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    Nahed Ismail MD, PhD

Authors
  1. Qiwei Yang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Archana Laknaur MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lelyand Elam BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nahed Ismail MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Larisa Gavrilova-Jordan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Lue MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael P. Diamond MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ayman Al-Hendy MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qiwei Yang PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Q., Laknaur, A., Elam, L. et al. Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids. Reprod. Sci. 23, 1314–1325 (2016). https://doi.org/10.1177/1933719116638186

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116638186

Keywords

Search

Navigation