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Abstract
Objective: This study examines how epigenetic mechanisms control the expression of the estrogen receptor (ER) gene in ovarian cancer, concentrating on DNA methylation, histone modifications, and non-coding RNAs in Iraqi population samples. Method: Bisulfite sequencing was used to measure the DNA methylation levels of the ER gene in tissue samples from ovarian cancer patients and healthy controls, and chromatin immunoprecipitation (ChIP) tests were used to examine histone alterations. Using RNA sequencing, important non-coding RNAs affecting ER pathways were found. The epigenetic variations between malignant and healthy tissues were assessed using comparative analysis. Results: The results showed that the ER gene was significantly more methylated in cancer tissues (67%) than in healthy samples (21%), which resulted in decreased cellular estrogen responses and increased proliferation. Oncogenes were activated by elevated histone H3K9 acetylation levels (1.7 AU vs. 0.8 AU), but tumor suppressor genes were inhibited by elevated H3K27 methylation (2.1 AU). These modifications draw attention to important epigenetic modifications that aid in the development of ovarian cancer. Novelty: By identifying region-specific epigenetic markers in ovarian cancer, this work highlights the significance of population-targeted research in enhancing cancer outcomes and provides insights into tailored therapy approaches.
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References
- A. Bird, "Perceptions of Epigenetics," Nature, vol. 447, no. 7143, pp. 396–398, 2007.
- H. Sung, et al., "Global Cancer Statistics," CA: A Cancer Journal for Clinicians, vol. 71, no. 3, pp. 7–30, 2021.
- X. Jiang, et al., "Estrogen and Ovarian Cancer," Journal of Cancer Research, vol. 8, no. 5, pp. 65–72, 2017.
- D. P. McDonnell and J. D. Norris, "Connections and Regulation of the Human Estrogen Receptor," Science, vol. 296, no. 5573, pp. 685–689, 2002.
- K. Huhtinen, et al., "Estrogen Signaling and Epithelial Ovarian Cancer," Molecular and Cellular Endocrinology, vol. 389, no. 1-2, pp. 438–446, 2014.
- A. P. Feinberg, "The Key Role of Epigenetics in Human Disease Prevention and Mitigation," Nature Biotechnology, vol. 36, no. 3, pp. 276–285, 2018.
- P. A. Jones, "Functions of DNA Methylation," Nature Reviews Genetics, vol. 13, no. 7, pp. 484–492, 2012.
- S. B. Baylin and P. A. Jones, "Epigenetic Determinants of Cancer," Cancer Discovery, vol. 6, no. 3, pp. 162–171, 2016.
- C. D. Allis and T. Jenuwein, "The Molecular Hallmarks of Epigenetic Control," Nature Reviews Genetics, vol. 17, no. 8, pp. 487–500, 2016.
- J. Krol, I. Loedige, and W. Filipowicz, "The Widespread Regulation of microRNA Biogenesis," Nature Reviews Genetics, vol. 11, no. 9, pp. 597–610, 2010.
- J. Rodriguez, "Epigenetic Control of Tumorigenesis," Trends in Molecular Medicine, vol. 23, no. 4, pp. 290–305, 2017.
- L. Zhao, et al., "Epigenetic Influence on Estrogen Receptor Expression," Journal of Cancer Epigenetics, vol. 5, no. 2, pp. 300–310, 2017.
- J. Chen, et al., "Epigenetic Modifications in Ovarian Cancer," Cancer Letters, vol. 454, pp. 443–454, 2019.
- W. Wagner and K. Carpenter, "Histone Acetylation and Methylation in Cancer Progression," Cancer Biology Journal, vol. 7, no. 1, pp. 20–25, 2012.
- C. J. Smith and J. D. Spence, "The Regional and Global Burden of Ovarian Cancer," Oncology Reviews, vol. 14, no. 1, 2020.
- A. Razin and R. Shemer, "DNA Methylation in Early Development," Human Molecular Genetics, vol. 4, suppl_1, pp. 1751–1756, 1995.
- P. M. Das and R. Singal, "DNA Methylation and Cancer," Journal of Clinical Oncology, vol. 22, no. 22, pp. 4632–4642, 2004.
- S. Kurdyukov and M. Bullock, "DNA Methylation Analysis: Choosing the Right Method," Biology, vol. 5, no. 1, pp. 3–10, 2016.
- J. R. Edwards, O. Yarychkivska, M. Boulard, and T. H. Bestor, "DNA Methylation and DNA Methyltransferases," Epigenetics & Chromatin, vol. 10, no. 1, pp. 1–10, 2017.
- R. Singal and G. D. Ginder, "DNA Methylation," Blood, The Journal of the American Society of Hematology, vol. 93, no. 12, pp. 4059–4070, 1999.
References
A. Bird, "Perceptions of Epigenetics," Nature, vol. 447, no. 7143, pp. 396–398, 2007.
H. Sung, et al., "Global Cancer Statistics," CA: A Cancer Journal for Clinicians, vol. 71, no. 3, pp. 7–30, 2021.
X. Jiang, et al., "Estrogen and Ovarian Cancer," Journal of Cancer Research, vol. 8, no. 5, pp. 65–72, 2017.
D. P. McDonnell and J. D. Norris, "Connections and Regulation of the Human Estrogen Receptor," Science, vol. 296, no. 5573, pp. 685–689, 2002.
K. Huhtinen, et al., "Estrogen Signaling and Epithelial Ovarian Cancer," Molecular and Cellular Endocrinology, vol. 389, no. 1-2, pp. 438–446, 2014.
A. P. Feinberg, "The Key Role of Epigenetics in Human Disease Prevention and Mitigation," Nature Biotechnology, vol. 36, no. 3, pp. 276–285, 2018.
P. A. Jones, "Functions of DNA Methylation," Nature Reviews Genetics, vol. 13, no. 7, pp. 484–492, 2012.
S. B. Baylin and P. A. Jones, "Epigenetic Determinants of Cancer," Cancer Discovery, vol. 6, no. 3, pp. 162–171, 2016.
C. D. Allis and T. Jenuwein, "The Molecular Hallmarks of Epigenetic Control," Nature Reviews Genetics, vol. 17, no. 8, pp. 487–500, 2016.
J. Krol, I. Loedige, and W. Filipowicz, "The Widespread Regulation of microRNA Biogenesis," Nature Reviews Genetics, vol. 11, no. 9, pp. 597–610, 2010.
J. Rodriguez, "Epigenetic Control of Tumorigenesis," Trends in Molecular Medicine, vol. 23, no. 4, pp. 290–305, 2017.
L. Zhao, et al., "Epigenetic Influence on Estrogen Receptor Expression," Journal of Cancer Epigenetics, vol. 5, no. 2, pp. 300–310, 2017.
J. Chen, et al., "Epigenetic Modifications in Ovarian Cancer," Cancer Letters, vol. 454, pp. 443–454, 2019.
W. Wagner and K. Carpenter, "Histone Acetylation and Methylation in Cancer Progression," Cancer Biology Journal, vol. 7, no. 1, pp. 20–25, 2012.
C. J. Smith and J. D. Spence, "The Regional and Global Burden of Ovarian Cancer," Oncology Reviews, vol. 14, no. 1, 2020.
A. Razin and R. Shemer, "DNA Methylation in Early Development," Human Molecular Genetics, vol. 4, suppl_1, pp. 1751–1756, 1995.
P. M. Das and R. Singal, "DNA Methylation and Cancer," Journal of Clinical Oncology, vol. 22, no. 22, pp. 4632–4642, 2004.
S. Kurdyukov and M. Bullock, "DNA Methylation Analysis: Choosing the Right Method," Biology, vol. 5, no. 1, pp. 3–10, 2016.
J. R. Edwards, O. Yarychkivska, M. Boulard, and T. H. Bestor, "DNA Methylation and DNA Methyltransferases," Epigenetics & Chromatin, vol. 10, no. 1, pp. 1–10, 2017.
R. Singal and G. D. Ginder, "DNA Methylation," Blood, The Journal of the American Society of Hematology, vol. 93, no. 12, pp. 4059–4070, 1999.