Epigenetics and MicroRNAs in Cancer

Ramassone, Alice; Pagotto, Sara; Veronese, Angelo; Visone, Rosa

doi:10.3390/ijms19020459

Cited by 128 publications

(90 citation statements)

References 293 publications

(202 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epigenetics and cancer has been tightly linked where reprograming the transcriptional circuitry by remodeling the three-dimensional structure of the genome is exploited by cancer cells to promote tumorigenesis [85,86]. Epigenetic mechanisms underlie the phenotypic plasticity of cells, and provide the foundation for oncogenic transformation [25].…”

Section: Epigenetics Gene Transcription Metabolism and Vdac1mentioning

confidence: 99%

The Mitochondrial Protein VDAC1 at the Crossroads of Cancer Cell Metabolism: The Epigenetic Link

Amsalem

Arif

Shteinfer‐Kuzmine

et al. 2020

Cancers

View full text Add to dashboard Cite

Carcinogenesis is a complicated process that involves the deregulation of epigenetics, resulting in cellular transformational events, such as proliferation, differentiation, and metastasis. Most chromatin-modifying enzymes utilize metabolites as co-factors or substrates and thus are directly dependent on such metabolites as acetyl-coenzyme A, S-adenosylmethionine, and NAD+. Here, we show that using specific siRNA to deplete a tumor of VDAC1 not only led to reprograming of the cancer cell metabolism but also altered several epigenetic-related enzymes and factors. VDAC1, in the outer mitochondrial membrane, controls metabolic cross-talk between the mitochondria and the rest of the cell, thus regulating the metabolic and energetic functions of mitochondria, and has been implicated in apoptotic-relevant events. We previously demonstrated that silencing VDAC1 expression in glioblastoma (GBM) U-87MG cell-derived tumors, resulted in reprogramed metabolism leading to inhibited tumor growth, angiogenesis, epithelial-mesenchymal transition and invasiveness, and elimination of cancer stem cells, while promoting the differentiation of residual tumor cells into neuronal-like cells. These VDAC1 depletion-mediated effects involved alterations in transcription factors regulating signaling pathways associated with cancer hallmarks. As the epigenome is sensitive to cellular metabolism, this study was designed to assess whether depleting VDAC1 affects the metabolism-epigenetics axis. Using DNA microarrays, q-PCR, and specific antibodies, we analyzed the effects of si-VDAC1 treatment of U-87MG-derived tumors on histone modifications and epigenetic-related enzyme expression levels, as well as the methylation and acetylation state, to uncover any alterations in epigenetic properties. Our results demonstrate that metabolic rewiring of GBM via VDAC1 depletion affects epigenetic modifications, and strongly support the presence of an interplay between metabolism and epigenetics.Cancers 2020, 12, 1031 2 of 25 cellular metabolic activity regulates transcriptional networks and cell-fate decisions via epigenetic programs involving metabolite-dependent effects on chromatin organization. Epigenetics refers to a change in chromatin that leads to the regulation of gene expression without alterations in the DNA sequence [6]. Epigenetic modifications include DNA methylation, and/or histone modifications by acetylation, ubiquitination, methylation, phosphorylation, sumoylation, glycosylation, and biotinylation, changes that play a critical role in many cellular processes [7][8][9][10][11][12][13]. The enzymes responsible for these modifications include histone acetyltransferases (HATs), histone deacetylases (HDACs), methyltransferases (KMTs), and demethylases (KDMs) [14][15][16].There is now an accumulation of evidence that the epigenome is sensitive to cellular metabolism and a link between metabolism and epigenetics [3][4][5][17][18][19] has been proposed, with epigenetics and gene transcription being influenced by products of metabolic pathways [...

show abstract

Section: Epigenetics Gene Transcription Metabolism and Vdac1mentioning

confidence: 99%

The Mitochondrial Protein VDAC1 at the Crossroads of Cancer Cell Metabolism: The Epigenetic Link

Amsalem

Arif

Shteinfer‐Kuzmine

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…the onset of cancer there are alterations that can unbalance the ratio between oncomiRNAs and tumor suppressor miRNAs fostering tumorigenesis. Deregulation of miRNAs expression can be established by alterations that affect their biogenesis, such as: (a) epigenetic modification on their regulatory regions; (b) changes in the activity of specific transcription factors; (c) alterations in processing enzymes involved in miRNAs' maturation steps (mainly Drosha and Dicer) (Rakheja et al, 2014;Lin and Gregory, 2015;Frixa et al, 2018;Ramassone et al, 2018).…”

Section: Micrornas As Potential Cancer Biomarkers In Tissues and In Bmentioning

confidence: 99%

Non-coding RNAs as Putative Biomarkers of Cancer-Associated Cachexia

Donzelli¹,

Farneti

Marucci

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

“…miR-449a) regulate HDAC expression. In certain types of malignancies, such as ovarian cancer or B-cell lymphoma, translocations generate aberrant fusion proteins, mutations or deletions of HAT coding genes (RAMASSONE, et al 2018).…”

Section: Epigenetic Modifications In Malignancymentioning

confidence: 99%

Epigenetics in disease etiopathogenesis

Glavaški

Stankov

2019

Genetika

View full text Add to dashboard Cite

2019): Epigenetics in disease etiopathogenesis.-Genetika, Vol 51, No.3, 975-994. The term epigenetics refers to heritable changes in gene expression that are not caused by modifications in DNA sequence. Epigenetic changes are DNA methylation, histone modifications, nucleosome positioning, and non-coding RNA (including microRNA) mediated modifications. Epigenetic mechanisms are involved in malignant diseases, imprinting defects, and some hereditary diseases. Recent research explained the role of epigenetic disorders in infections, autoimmune, neurodegenerative and bone diseases, as well as in psoriasis, endometriosis, and polycystic ovary syndrome. Epigenetic modifications have a potential clinical application as diagnostic and prognostic biomarkers, and also as therapeutic targets in oncology, endocrinology, cardiology, and neuropsychiatry. Stress, anxiety, depression, emotions and many other psychological factors may affect epigenetic mechanisms. Influence of preconception parental stress exposure transmits to the next generation through epigenetic changes, as direct results of prenatal and postnatal environmental factors. Epigenetic changes identify environmental factors which affect health and cause disease onset. Milk is the sophisticated system of communication between mother and infant, operating via epigenetic mechanisms. Lifelong consumption of bovine milk causes epigenetic disorders. Recent studies provide important information about the role of bioactive dietary nutrients which modify DE SARIO, A. (2009): Clinical and molecular overview of inherited disorders resulting from epigenomic dysregulation. Eur. J. Med. Genet., 52(6): 363-372.

show abstract

Epigenetics and MicroRNAs in Cancer

Cited by 128 publications

References 293 publications

The Mitochondrial Protein VDAC1 at the Crossroads of Cancer Cell Metabolism: The Epigenetic Link

The Mitochondrial Protein VDAC1 at the Crossroads of Cancer Cell Metabolism: The Epigenetic Link

Non-coding RNAs as Putative Biomarkers of Cancer-Associated Cachexia

Epigenetics in disease etiopathogenesis

Contact Info

Product

Resources

About