Topic Editors

Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary

Cancer Stem Cells, DNA Methylation and DNA Sequences: Their Diagnostic and Therapeutical Applications

Abstract submission deadline
30 September 2024
Manuscript submission deadline
30 November 2024
Viewed by
5674

Topic Information

Dear Colleagues,

DNA methylation is an essential epigenetic mechanism for controlling gene expression in both embryonic and adult stem cells. There is a fine-tuned balance between the regulation of gene activation and repression during normal cellular activity, and either hypo- or hypermethylation could induce the expression or inhibition of genes, respectively. Changes in methylation status are acknowledged to be hallmarks for cancer initiation and progression, with the potential to transform normal stem cells into a cancer stem cell (CSC) phenotype. The basic function of the immune system is to provide the host with protection from invading foreign antigens in parallel with the state of self-tolerance, i.e., maintaining its unique antigenic profile. Cellular structures such as nuclei and mitochondria house the vast bulk of DNA. Changes in DNA sequences have gained attention as potential biomarkers since they can be detected as extracellular cell-free DNA (cfDNA) in a wide range of diseases, including cancer. Recently, cfDNA testing has seen a resurgence due to the widespread use of liquid biopsies and the growing need for disease screening, activity monitoring, and drug response assessments. Studies on the immunological effects of cfDNA, in addition to their immunomodulatory or therapeutic advantages, are still in their infancy. The main aim of this Special Issue (Topic) is to discuss the impact of aberrant DNA methylation statuses on CSC functions, including self-renewal, differentiation, drug resistance, and metastasis formation, in addition to analyzing recent findings on the role of different DNA-sensing receptors in the recognition of foreign or self-DNA sequences as potent danger-associated molecular patterns. Further, emphasizing the immunomodulatory as well as pro- and anti-tumor capacities of different DNA sequences, and thus their subsequent potential for anticancer therapy, this Special Issue (Topic) also intends to summarize the results of recent experimental studies.

Dr. Ferenc Sipos
Dr. Györgyi Műzes
Topic Editors

Keywords

  • cancer stem cells
  • DNA methylation
  • epigenome
  • drug resistance
  • metastasis
  • self-renewal
  • hypermethylation
  • hypomethylation
  • DNA sequence
  • cell-free DNA
  • DNA sensing
  • methylation signatures
  • differentially methylated probes or regions
  • diagnostic performance
  • therapy
  • liquid biopsy
  • DNA methylation technologies
  • tissue of origin (TOO)
  • CpG oligonucleotides
  • toll-like receptor 9
  • absent in melanoma-2
  • cyclic GMP–AMP synthase
  • tumor microenvironment

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomedicines
biomedicines
4.7 3.7 2013 15.4 Days CHF 2600 Submit
Cancers
cancers
5.2 7.4 2009 17.9 Days CHF 2900 Submit
Cells
cells
6.0 9.0 2012 16.6 Days CHF 2700 Submit
Journal of Clinical Medicine
jcm
3.9 5.4 2012 17.9 Days CHF 2600 Submit
Pharmaceutics
pharmaceutics
5.4 6.9 2009 14.2 Days CHF 2900 Submit
Reports
reports
0.9 - 2018 20.6 Days CHF 1400 Submit

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Published Papers (4 papers)

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27 pages, 2265 KiB  
Review
Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy
by Ferenc Sipos and Györgyi Műzes
Biomedicines 2024, 12(2), 386; https://doi.org/10.3390/biomedicines12020386 - 07 Feb 2024
Viewed by 838
Abstract
Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the [...] Read more.
Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the SIRT family have the ability to govern embryonic, hematopoietic, and other adult stem cells in certain tissues and cell types in distinct ways. Likewise, they can have both pro-tumor and anti-tumor effects on cancer stem cells, contingent upon the specific tissue from which they originate. The impact of autophagy on cancer stem cells, which varies depending on the specific circumstances, is a very intricate phenomenon that has significant significance for clinical and therapeutic purposes. SIRTs exert an impact on the autophagy process, whereas autophagy reciprocally affects the activity of certain SIRTs. The mechanism behind this connection in cancer stem cells remains poorly understood. This review presents the latest findings that position SIRTs at the point where cancer cells and autophagy interact. Our objective is to highlight the various roles of distinct SIRTs in cancer stem cell-related functions through autophagy. This would demonstrate their significance in the genesis and recurrence of cancer and offer a more precise understanding of their treatment possibilities in relation to autophagy. Full article
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23 pages, 1454 KiB  
Review
Unravelling the Role of PARP1 in Homeostasis and Tumorigenesis: Implications for Anti-Cancer Therapies and Overcoming Resistance
by Taylor Lovsund, Fatemeh Mashayekhi, Amira Fitieh, James Stafford and Ismail Hassan Ismail
Cells 2023, 12(14), 1904; https://doi.org/10.3390/cells12141904 - 21 Jul 2023
Viewed by 1326
Abstract
Detailing the connection between homeostatic functions of enzymatic families and eventual progression into tumorigenesis is crucial to our understanding of anti-cancer therapies. One key enzyme group involved in this process is the Poly (ADP-ribose) polymerase (PARP) family, responsible for an expansive number of [...] Read more.
Detailing the connection between homeostatic functions of enzymatic families and eventual progression into tumorigenesis is crucial to our understanding of anti-cancer therapies. One key enzyme group involved in this process is the Poly (ADP-ribose) polymerase (PARP) family, responsible for an expansive number of cellular functions, featuring members well established as regulators of DNA repair, genomic stability and beyond. Several PARP inhibitors (PARPi) have been approved for clinical use in a range of cancers, with many more still in trials. Unfortunately, the occurrence of resistance to PARPi therapy is growing in prevalence and requires the introduction of novel counter-resistance mechanisms to maintain efficacy. In this review, we summarize the updated understanding of the vast homeostatic functions the PARP family mediates and pin the importance of PARPi therapies as anti-cancer agents while discussing resistance mechanisms and current up-and-coming counter-strategies for countering such resistance. Full article
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21 pages, 5425 KiB  
Article
Interferon-Alpha Decreases Cancer Stem Cell Properties and Modulates Exosomes in Malignant Melanoma
by María Belén García-Ortega, Ernesto Aparicio, Carmen Griñán-Lisón, Gema Jiménez, Elena López-Ruiz, José Luis Palacios, Gloria Ruiz-Alcalá, Cristina Alba, Antonio Martínez, Houria Boulaiz, Macarena Perán, Michael Hackenberg, José Bragança, Sofia M. Calado, Juan A. Marchal and María Ángel García
Cancers 2023, 15(14), 3666; https://doi.org/10.3390/cancers15143666 - 18 Jul 2023
Viewed by 1539
Abstract
Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable [...] Read more.
Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma. Full article
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13 pages, 708 KiB  
Article
Aberrant AHRR, ADAMTS2 and FAM184 DNA Methylation: Candidate Biomarkers in the Oral Rinse of Heavy Smokers
by Hernán Guillermo Hernández, Gloria Cristina Aranzazu-Moya and Efraín Hernando Pinzón-Reyes
Biomedicines 2023, 11(7), 1797; https://doi.org/10.3390/biomedicines11071797 - 23 Jun 2023
Viewed by 975
Abstract
Objective. To identify DNA methylation patterns of heavy smokers in oral rinse samples. Methods. Genome-wide DNA methylation data was imported from Gene Expression Omnibus GSE70977 using the GEOquery package. Two independent sets were analyzed: (a) 71 epigenomes of cancer-free subjects (heavy smokers n [...] Read more.
Objective. To identify DNA methylation patterns of heavy smokers in oral rinse samples. Methods. Genome-wide DNA methylation data was imported from Gene Expression Omnibus GSE70977 using the GEOquery package. Two independent sets were analyzed: (a) 71 epigenomes of cancer-free subjects (heavy smokers n = 37 vs. non-smokers n = 31); for concordance assessment (b) 139 oral-cancer patients’ epigenomes (heavy smokers n = 92 vs. non-smokers n = 47). Differential DNA methylation for CpG positions and at the regional level was determined using Limma and DMRcate Bioconductor packages. The linear model included sex, age, and alcohol consumption. The statistical threshold was set to p < 0.05. Functional gene prioritization analysis was performed for gene-targeted analysis. Results. In individuals without cancer and heavy smokers, the FAM184B gene was found with two CpG positions differentially hypermethylated (p = 0.012 after FDR adjustment), in a region of 48 bp with an absolute methylation difference >10% between groups (p = 1.76 × 10−8). In the analysis corresponding to oral-cancer patients, we found AHRR differentially hypomethylated cancer patients, but also in subjects without oral cancer in the targeted analyses. Remarkably, ADAMTS2 was found differentially hypermethylated in heavy smokers without a diagnosis of cancer in two consecutive probes cg05575921 (p = 3.13 × 10−7) and cg10208897 (p = 1.36 × 10−5). Conclusions: Differentially methylated AHRR, ADAMTS2, and FAM184B genes are biomarker candidates in oral rinse samples. Full article
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