Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis
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 eutop...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3492 |
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| author | Sarah Brunty Kristeena Ray Wright Brenda Mitchell Nalini Santanam |
| author_facet | Sarah Brunty Kristeena Ray Wright Brenda Mitchell Nalini Santanam |
| author_sort | Sarah Brunty |
| collection | DOAJ |
| description | 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 <i>PHF19</i> (<i>p</i> = 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. |
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| id | doaj.art-7974f7b40dc34adfa8e005d3ed4b24ff |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:50:24Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7974f7b40dc34adfa8e005d3ed4b24ff2023-11-21T13:08:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227349210.3390/ijms22073492Peritoneal Modulators of EZH2-miR-155 Cross-Talk in EndometriosisSarah Brunty0Kristeena Ray Wright1Brenda Mitchell2Nalini Santanam3Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USADepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USADepartment of Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USADepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USAActivation 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 <i>PHF19</i> (<i>p</i> = 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.https://www.mdpi.com/1422-0067/22/7/3492endometriosisepigeneticsEZH2microRNA |
| spellingShingle | Sarah Brunty Kristeena Ray Wright Brenda Mitchell Nalini Santanam Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis International Journal of Molecular Sciences endometriosis epigenetics EZH2 microRNA |
| title | Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis |
| title_full | Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis |
| title_fullStr | Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis |
| title_full_unstemmed | Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis |
| title_short | Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis |
| title_sort | peritoneal modulators of ezh2 mir 155 cross talk in endometriosis |
| topic | endometriosis epigenetics EZH2 microRNA |
| url | https://www.mdpi.com/1422-0067/22/7/3492 |
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