Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis

被引:13
作者
Brunty, Sarah [1 ]
Ray Wright, Kristeena [1 ]
Mitchell, Brenda [2 ]
Santanam, Nalini [1 ]
机构
[1] Marshall Univ, Joan C Edwards Sch Med, Dept Biomed Sci, Huntington, WV 25755 USA
[2] Marshall Univ, Joan C Edwards Sch Med, Dept Obstet & Gynecol, Huntington, WV 25755 USA
基金
芬兰科学院;
关键词
endometriosis; epigenetics; EZH2; microRNA; REGULATORY T-CELLS; HISTONE METHYLTRANSFERASE ACTIVITY; DNA METHYLATION; DOWN-REGULATION; PRC2; COMPLEX; POLYCOMB; FLUID; PATHOGENESIS; JARID2; EZH2;
D O I
10.3390/ijms22073492
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of trimethylation of histone 3 lysine 27 (H3K27me3) by EZH2, a component of the Polycomb repressive complex 2 (PRC2), is suggested to play a role in endometriosis. However, the mechanism by which this complex is dysregulated in endometriosis is not completely understood. Here, using eutopic and ectopic tissues, as well as peritoneal fluid (PF) from IRB-approved and consented patients with and without endometriosis, the expression of PRC2 complex components, JARID2, miR-155 (known regulators of EZH2), and a key inflammatory modulator, FOXP3, was measured. A higher expression of EZH2, H3K27me3, JARID2, and FOXP3 as well as miR-155 was noted in both the patient tissues and in endometrial PF treated cells. Gain-or-loss of function of miR-155 showed an effect on the PRC2 complex but had little effect on JARID2 expression, suggesting alternate pathways. Chromatin immunoprecipitation followed by qPCR showed differential expression of PRC2 complex proteins and its associated binding partners in JARID2 vs. EZH2 pull down assays. In particular, endometriotic PF treatment increased the expression of PHF19 (p = 0.0474), a gene silencer and co-factor that promotes PRC2 interaction with its targets. Thus, these studies have identified the potential novel crosstalk between miR-155-PRC2 complex-JARID2 and PHF19 in endometriosis, providing an opportunity to test other epigenetic targets in endometriosis.
引用
收藏
页数:20
相关论文
共 78 条
  • [1] Selective inhibition of prostaglandin E2 receptors EP2 and EP4 modulates DNA methylation and histone modification machinery proteins in human endometriotic cells
    Arosh, Joe A.
    Lee, JeHoon
    Starzinski-Powitz, Anna
    Banu, Sakhila K.
    [J]. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2015, 409 (0C) : 51 - 58
  • [2] Disruption of FOXP3-EZH2 Interaction Represents a Pathobiological Mechanism in Intestinal Inflammation
    Bamidele, Adebowale O.
    Svingen, Phyllis A.
    Sagstetter, Mary R.
    Sarmento, Olga F.
    Gonzalez, Michelle
    Braga Neto, Manuel B.
    Kugathasan, Subra
    Lomberk, Gwen
    Urrutia, Raul A.
    Faubion, William A., Jr.
    [J]. CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 2019, 7 (01): : 55 - 71
  • [3] Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial
    Bedaiwy, MA
    Falcone, T
    Sharma, RK
    Goldberg, JM
    Attaran, M
    Nelson, DR
    Agarwal, A
    [J]. HUMAN REPRODUCTION, 2002, 17 (02) : 426 - 431
  • [4] Regulatory T cells and other leukocytes in the pathogenesis of endometriosis
    Berbic, M.
    Fraser, I. S.
    [J]. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2011, 88 (02) : 149 - 155
  • [5] Perceptions of epigenetics
    Bird, Adrian
    [J]. NATURE, 2007, 447 (7143) : 396 - 398
  • [6] Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations
    Bitler, Benjamin G.
    Aird, Katherine M.
    Zhang, Rugang
    [J]. MOLECULAR & CELLULAR ONCOLOGY, 2016, 3 (01):
  • [7] Peritoneal fluid modifies the microRNA expression profile in endometrial and endometriotic cells from women with endometriosis
    Braza-Boils, Aitana
    Salloum-Asfar, Salam
    Mari-Alexandre, Josep
    Belen Arroyo, Ana
    Gonzalez-Conejero, Rocio
    Barcelo-Molina, Moises
    Garcia-Oms, Javier
    Vicente, Vicente
    Estelles, Amparo
    Gilabert-Estelles, Juan
    Martinez, Constantino
    [J]. HUMAN REPRODUCTION, 2015, 30 (10) : 2292 - 2302
  • [8] Peritoneal Fluid Reduces Angiogenesis-Related MicroRNA Expression in Cell Cultures of Endometrial and Endometriotic Tissues from Women with Endometriosis
    Braza-Boils, Aitana
    Gilabert-Estelles, Juan
    Ramon, Luis A.
    Gilabert, Juan
    Mari-Alexandre, Josep
    Chirivella, Melitina
    Espana, Francisco
    Estelles, Amparo
    [J]. PLOS ONE, 2013, 8 (04):
  • [9] Targeting PCL3/PHF19 as an alternative therapeutic strategy to EZH2 inhibition in PRC2-deregulated cancers
    Brien, Gerard L.
    Jerman, Emilia
    Campbell, Matthew
    Adrian, Bracken P.
    [J]. CANCER RESEARCH, 2013, 73
  • [10] Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation
    Brien, Gerard L.
    Gambero, Guillermo
    O'Connell, David J.
    Jerman, Emilia
    Turner, Siobhan A.
    Egan, Chris M.
    Dunne, Eiseart J.
    Jurgens, Maike C.
    Wynne, Kieran
    Piao, Lianhua
    Lohan, Amanda J.
    Ferguson, Neil
    Shi, Xiaobing
    Sinha, Krishna M.
    Loftus, Brendan J.
    Cagney, Gerard
    Bracken, Adrian P.
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (12) : 1273 - +