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Targeting Epigenetic Network in Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 7738

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Dr. Katarzyna Lubecka-Gajewska

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Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 92215 Lodz, Poland
Interests: cancer cell biology; cancer biomarkers; anti-cancer therapy; cancer epigenetics; DNA methylation; nutritional epigenomics
Special Issues, Collections and Topics in MDPI journals

Dr. Agnieszka Kaufman-Szymczyk

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Dear Colleagues,

As many sporadic cancer cases have been shown to be the result of a variety of modifiable lifestyle factors, including poor dietary habits, sedentary lifestyle, obesity, cigarette smoking, and exogenous hormones, a dysregulated epigenetic code seems to play an important role in sporadic cancer development. Three main epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA mechanisms, are concerted in the epigenetic network to determine the transcriptional activity of certain genes. In cancer, aberrant epigenetic mechanisms may lead to the silencing of tumor suppressor genes and concomitantly to overexpression of oncogenes and prometastatic genes. Many tumor suppressor genes and oncogenes have been shown to act as negative and positive regulators of intracellular oncogenic signaling pathways, respectively. Due to the increasing incidence rates of tumors and their heterogeneity, there is a desperate need for the development of new effective strategies of diagnosis, prevention, and therapy, including epigenetic diagnostic biomarkers, epigenetic chemoprevention, and epigenetic anti-cancer therapy. This Special Issue plans to give an overview of the most recent advances in the field of medical epigenetics in cancer and its application as a potential source of cancer biomarkers and anti-cancer therapies. Potential topics include, but are not limited to:

DNA methylation in cancer;
Histone modifications in cancer;
Non-coding RNA mechanisms in cancer;
RNA methylation in cancer;
Epigenetic cancer biomarkers;
Epigenetic anti-cancer therapy;
Epigenetic chemoprevention.

Dr. Katarzyna Lubecka-Gajewska
Dr. Agnieszka Kaufman-Szymczyk
Guest Editors

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Keywords

epigenetics in cancer
DNA methylation in cancer
histone modifications in cancer
non-coding RNA mechanisms in cancer
miRNAs in cancer
RNA methylation in cancer
epigenetic cancer biomarkers
epigenetic anti-cancer therapy
epigenetic chemoprevention

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Research

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14 pages, 1036 KiB

Open AccessArticle

Constitutional BRCA1 and MGMT Methylation Are Significant Risk Factors for Triple-Negative Breast Cancer and High-Grade Serous Ovarian Cancer in Saudi Women

by Nisreen Al-Moghrabi, Maram Al-Showimi, Amal Alqahtani, Osama Almalik, Hamed Alhusaini, Ghdah Almalki, Ajawhara Saad and Elaf Alsunayi

Int. J. Mol. Sci. 2024, 25(6), 3108; https://doi.org/10.3390/ijms25063108 - 7 Mar 2024

Cited by 1 | Viewed by 1736

Abstract

Breast cancer (BC) and ovarian cancer (OC) are rapidly increasing in Saudi Arabia. BRCA1 and MGMT epimutations have been linked to a higher risk of these malignancies. The present research investigated the impact of these epimutations on the prevalence of BC and OC among Saudi women. DNA methylation was evaluated using methylation-specific PCR, whereas mRNA expression levels were assessed using qRT-PCR. We evaluated white blood cell (WBC)–BRCA1 methylation in 1958 Saudi women (908 BC patients, 223 OC patients, and 827 controls). MGMT methylation was determined in 1534 of the 1958 women (700 BC patients, 223 OC patients, and 611 controls). BRCA1 methylation was detected in 8.6% of the controls and 11% of the BC patients. This epimutation was linked to 13.8% of the early-onset BC patients (p = 0.003) and 20% of the triple-negative breast cancer (TNBC) patients (p = 0.0001). BRCA1 methylation was also detected in 14% of the OC patients (p = 0.011), 19.4% of patients aged <55 years (p = 0.0007), and 23.4% of high-grade serous ovarian cancer (HGSOC) patients. In contrast, the BRCA1 mutation was detected in 24% of the OC patients, 27.4% of patients aged ≥55 years, and 26.7% of the HGSOC patients. However, MGMT methylation was detected in 10% of the controls and 17.4% of the BC patients (p = 0.0003). This epimutation was linked to 26.4% of the late-onset BC patients (p = 0.0001) and 11% of the TNBC patients. MGMT methylation was also found in 15.2% of the OC patients (p = 0.034) and 19.1% of HGSOC patients (p = 0.054). Furthermore, 36% of the BRCA1-methylated patients and 34.5% of the MGMT-methylated patients had a family history of cancer, including breast and ovarian cancer. Notably, BRCA1 and MGMT mRNA levels were greater in the WBC RNA of the BC patients and cancer-free methylation carriers than in that of the OC patients. Our data indicate that BRCA1 and MGMT epimutations significantly contribute to the development of breast cancer and ovarian cancer in Saudi cancer patients. These blood-based biomarkers could help identify female patients at high risk of developing TNBC and HGSOC at an early age. Full article

(This article belongs to the Special Issue Targeting Epigenetic Network in Cancer)

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14 pages, 2682 KiB

Open AccessArticle

Histone Methyltransferases G9a/Ehmt2 and GLP/Ehmt1 Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma

by Barbara Kunzler Souza, Natalia Hogetop Freire, Thiago Santos Monteiro, Alice Laschuk Herlinger, Mariane Jaeger, Matheus G. S. Dalmolin, Caroline Brunetto de Farias, Lauro Gregianin, André T. Brunetto, Algemir L. Brunetto, Carol J. Thiele and Rafael Roesler

Int. J. Mol. Sci. 2023, 24(20), 15242; https://doi.org/10.3390/ijms242015242 - 17 Oct 2023

Cited by 2 | Viewed by 1863

Abstract

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/Ehmt1 gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types. Herein, we evaluated the role of G9a in two solid pediatric tumors: neuroblastoma (NB) and Ewing sarcoma (ES). Our results show that G9a/Ehmt2 and GLP/Ehmt1 expression is higher in tumors with poorer prognosis, including St4 International Neuroblastoma Staging System (INSS) stage, MYCN amplified NB, and metastatic ES. Importantly, higher G9a and GLP levels were associated with shorter patient overall survival (OS) in both NB and ES. Moreover, pharmacological inhibition of G9a/GLP reduced cell viability in NB and ES cells. These findings suggest that G9a and GLP are associated with more aggressive NB and ES tumors and should be further investigated as being epigenetic targets in pediatric solid cancers. Full article

(This article belongs to the Special Issue Targeting Epigenetic Network in Cancer)

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Review

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19 pages, 1598 KiB

Open AccessReview

Lunasin and Its Epigenetic Impact in Cancer Chemoprevention

by Agnieszka Kaufman-Szymczyk, Wiktoria Kaczmarek, Krystyna Fabianowska-Majewska and Katarzyna Lubecka-Gajewska

Int. J. Mol. Sci. 2023, 24(11), 9187; https://doi.org/10.3390/ijms24119187 - 24 May 2023

Cited by 2 | Viewed by 3056

Abstract

Cancer diseases are a leading cause of death worldwide. Therefore, it is pivotal to search for bioactive dietary compounds that can avert tumor development. A diet rich in vegetables, including legumes, provides chemopreventive substances, which have the potential to prevent many diseases, including cancer. Lunasin is a soy-derived peptide whose anti-cancer activity has been studied for over 20 years. The results of the previous research have shown that lunasin inhibits histone acetylation, regulates the cell cycle, suppresses proliferation and induces apoptosis of cancer cells. Thus, lunasin seems to be a promising bioactive anti-cancer agent and a potent epigenetic modulator. The present review discusses studies of the underlying molecular mechanisms and new perspectives on lunasin application in epigenetic prevention and anti-cancer therapy. Full article

(This article belongs to the Special Issue Targeting Epigenetic Network in Cancer)

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