Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis

Casalino, Laura; Verde, Pasquale

doi:10.3390/genes11080922

Cited by 52 publications

(32 citation statements)

References 143 publications

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“…There is growing evidence that altered DNA methylation contributes to the occurrence of several diseases (36). Different types of cancers and allergic, immunological, and inflammatory diseases are closely associated with the epigenetic changes of DNA (37)(38)(39). Besides tumors, the main class of diseases associated with epigenetic modifications is neurodegenerative disease (40).…”

Section: Dna Methylationmentioning

confidence: 99%

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

et al. 2021

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Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome–brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed.

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Section: Dna Methylationmentioning

confidence: 99%

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

et al. 2021

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“…Generally, methylation of CpG islands limits binding of transcription factors at gene promoters. Global CpG hypomethylation is known to occur in human cancers and precancerous conditions, although hypermethylation is also observed at distinct loci [ 76 ] (reviewed in [ 77 ]). This has led to suggestions that hypomethylation enhances genetic instability and malignant transformation, e.g., by the activation of oncogenes [ 78 ] and increased genomic rearrangements due to activation of transposable elements that are normally silenced within heterochromatin [ 79 ].…”

Section: Is There a Link Between Active Demethylation And Malignant Transformation?mentioning

confidence: 99%

Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies

Oliński

Slupphaug

Foksiński

et al. 2021

IJMS

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DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Furthermore, uracil generated by deamination of cytosine in DNA is not always damage as it is also an intermediate in normal somatic hypermutation (SHM) and class shift recombination (CSR) at the Ig locus of B-cells in adaptive immunity. Many of the modifications alter base-pairing properties and may thus cause replicative and transcriptional mutagenesis. The best known and most studied epigenetic mark in DNA is 5-methylcytosine (5mC), generated by a methyltransferase that uses SAM as methyl donor, usually in CpG contexts. Oxidation products of 5mC are now thought to be intermediates in active demethylation as well as epigenetic marks in their own rights. The aim of this review is to describe the endogenous processes that surround the generation and removal of the most common types of DNA nucleobase modifications, namely, uracil and certain epigenetic modifications, together with their role in the development of hematological malignances. We also discuss what dictates whether the presence of an altered nucleobase is defined as damage or a natural modification.

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“…Oncogenes dominate the mechanisms of cellular transformation via signal transduction that releases extracellular messages to the nucleus, resulting in variational cellular transcriptional patterns (3). Genetic modifications that break the balance between oncogenes and tumor suppressors can disturb the cellular signaling pathways, causing initiation of neoplastic properties (4).…”

Section: Introductionmentioning

confidence: 99%

MCTS1 promotes invasion and metastasis of oral cancer by modifying the EMT process

Huang¹,

Qiao²,

Li³

et al. 2021

Ann Transl Med

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Background: The oncogene, malignant T-cell-amplified sequence 1 (MCTS1), has been found to be highly expressed in a variety of cancer cell lines. It has been shown to be involved in cell cycle progression and to confer a growth advantage for lymphomas and breast cancer. Nevertheless, the role of MCTS1 in contributing to the development of oral cancer remains elusive.Methods: We analyzed the gene expression profiles of MCTS1 in normal oral keratinocytes and cancerous cells. Cellular proliferation, invasion, and migration experiments were performed to detect the effect of MCTS1 on the biological evolution of oral cancer. The in vitro results were verified by the in vivo lymphatic metastasis test. The underlying mechanism of MCTS1 in promoting oral cancer invasion and metastasis correlated with the epithelial-mesenchymal transition (EMT) process as revealed by western blotting. Results:The results showed that MCTS1 was aberrantly expressed in oral cancer cells. MCTS1 overexpression significantly promoted tumor cell growth, proliferation, migration, and invasion. MCTS1mediated lymphatic metastasis was verified in vivo using an intraplantar tumor model. Biomarkers associated with EMT progression were positively or negatively regulated upon knockdown or overexpression of MCTS1, respectively.Conclusions: Higher MCTS1 expression in oral cancer may be connected with an unfavorable prognosis due to involvement of MCTS1. MCTS1 potentiates the growth and proliferation of oral cancer cells and subsequent metastasis by regulating cell cycle and modifying the EMT process.

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Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis

Cited by 52 publications

References 143 publications

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies

MCTS1 promotes invasion and metastasis of oral cancer by modifying the EMT process

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