Histone modifications: A review about the presence of this epigenetic phenomenon in carcinogenesis

Chrun, Emanuely Silva; Modolo, Filipe; Daniel, Filipe Ivan

doi:10.1016/j.prp.2017.06.013

Cited by 74 publications

(44 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A nucleosome is composed of a segment of DNA, which is wrapped around an octamer of histone protein cores composed of two copies of each of the protein histones H2A, H2B, H3, and H4 [73,74]. Thousands of nucleosome units highly compact into a structure called chromatin [17,75].…”

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

“…Thousands of nucleosome units highly compact into a structure called chromatin [17,75]. Several translational modifications occur at the N-terminal domains of the histones, e.g., acetylation, methylation, phosphorylation, and ubiquitination, which regulate important cellular processes, including DNA repair, chromatin structure, gene expression, and DNA replication [74]. AFB1 exposure can alter the pattern of modifications in histones, resulting in an increase or repression of genes, facilitating the development of cancer, such as HCC [76].…”

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

“…The most common modifications in histones regulated by AFB1 are methylation and acetylation [74]. Methylation is catalyzed by enzymes called histone methyltransferases, which add the methyl group into the lysine of the histones H3 and H4, occurring as three different forms, including mono-, di-, or trimethylation.…”

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

“…Histone acetyltransferases, which catalyze the addition of the acetyl group, and the histone deacetylase (HDAC) enzymes, which remove the acetyl group, are the major enzymes involved in this dynamic process [73,79]. The increased expression of HDACs causes the hypoacetylation of histone H3, leading to the repression of the silencing of specific tumor suppressor genes, such as p21, inducing the differentiation and proliferation of liver tumor cells [74,80,81].…”

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

See 3 more Smart Citations

The Carcinogenicity of Aflatoxin B1

Li¹,

Liu²

2020

Aflatoxin B1 Occurrence, Detection and Toxicological Effects

View full text Add to dashboard Cite

Aflatoxins are a class of carcinogenic mycotoxins, products of Aspergillus fungi, which are known contaminants in a large portion of the world's food supply. Aflatoxin B1 (AFB1) is the most potent toxin, which has been strongly linked to the development of hepatocellular carcinoma (HCC), especially given coinfection with hepatitis B virus (HBV). AFB1 is catalyzed by cytochrome P450 (CYP450) into aflatoxin B1-8,9-exo-epoxide to form DNA adducts, which leads to carcinogenesis by disrupting DNA repair. AFB1-induced DNA damage is also caused by the production of excessive ROS, leading to the oxidation of DNA bases. The majority of AFB1related to HCC carry G-toT transversion of p53 gene. When the p53 gene is mutated, it shows a "gain of oncogenic function." In addition, epigenetic alterations may potentially be beneficial for the treatment of HCC, because the epigenetic changes are reversible. This chapter will provide important information on the carcinogenicity of AFB1, including DNA damage checkpoint response and epigenetic alteration.

show abstract

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

Section: Afb1 and Epigenetic Alterationmentioning

confidence: 99%

See 2 more Smart Citations

The Carcinogenicity of Aflatoxin B1

Li¹,

Liu²

2020

Aflatoxin B1 Occurrence, Detection and Toxicological Effects

View full text Add to dashboard Cite

show abstract

“…HDACi may cause cell cycle arrest, apoptosis, anti-angiogenesis and immune modulation. Notably, tumor cells are usually more sensitive to HDACi than normal cells (Chrun et al, 2017;Haberland et al, 2009). But, the underlying mechanism has not yet been fully exposed.…”

Section: Introductionmentioning

confidence: 99%

Targeting histones for degradation in cancer cells as a novel strategy in cancer treatment

Zhu

Jiang

Фан

et al. 2018

Sci. China Life Sci.

View full text Add to dashboard Cite

The anticancer therapies with the joint treatment of a histone deacetylase (HDAC) inhibitor and a DNA-damaging approach are actively under clinical investigations, but the underlying mechanism is unclear. Histone homeostasis is critical to genome stability, transcriptional accuracy, DNA repair process, senescence, and survival. We have previously demonstrated that the HDAC inhibitor, trichostatin A (TSA), could promote the degradation of the core histones induced by γ-radiation or the DNAalkylating agent methyl methanesulfonate (MMS) in non-cancer cells, including mouse spermatocyte and embryonic fibroblast cell lines. In this study, we found that the joint treatment by TSA and MMS induced the death of the cultured cancer cells with an additive effect, but induced degradation of the core histones synergistically in these cells. We then analyzed various combinations of other HDAC inhibitors, including suberoylanilide hydroxamic acid and valproate sodium, with MMS or other DNAdamaging agents, including etoposide and camptothecin. Most of these combined treatments induced cell death additively, but all the tested combinations induced degradation of the core histones synergistically. Meanwhile, we showed that cell cycle arrest might not be a primary consequence for the joint treatment of TSA and MMS. Given that clinic treatments of cancers jointly with an HDAC inhibitor and a DNA-damaging approach often show synergistic effects, histone degradation might more accurately underlie the synergistic effects of these joint treatments in clinic applications than other parameters, such as cell death and cell cycle arrest. Thus, our studies might suggest that the degradation of the core histones can serve as a new target for the development of cancer therapies. HDAC, histone deacetylase inhibitor, DNA damage, anticancer agent, histone degradation Citation:Yin, Y., Zhu, Q., Jiang, T., Fan, L., and Qiu, X. (2019). Targeting histones for degradation in cancer cells as a novel strategy in cancer treatment. Sci

show abstract

Epigenetic Therapies in the Precision Medicine Era

Leite

Oliveira

Cunha

et al. 2020

Advanced Therapeutics

View full text Add to dashboard Cite

The elucidation of the 3D structure of DNA revolutionized modern science and created the basis for the field of molecular biology. The advent of DNA sequencing, and further refinement with Next‐Generation Sequencing (NGS) techniques, has made possible the enormous accumulation of data, which are useful for understanding the molecular mechanisms associated to various complex and rare diseases. Thanks to these advances, today it is known that several mechanisms regulate gene expression without the occurrence of mutations in the genome, a phenomenom known as Epigenetics and Epigenomics. The main mechanisms involved are DNA methylation, histone modifications, and non‐coding RNA transcription. The knowledge of these mechanisms applied to biomedicine has enabled the emergence of several fields, especially precision medicine, which is based on the genetic and epigenetic profiles of patients applied to personalized diagnostics and treatments. In this review, the history of the scientific advances that have enabled the development of precision medicine will be discussed, with a focus in epigenetics. Moreover, several molecules that have been approved for use or have the potential in epigenetic therapies (epidrugs) will also be discussed here, those of which act on targets responsible for maintaining the correct epigenetic pattern or correcting wrong patterns in diseases.

show abstract

Histone modifications: A review about the presence of this epigenetic phenomenon in carcinogenesis

Cited by 74 publications

References 141 publications

The Carcinogenicity of Aflatoxin B1

The Carcinogenicity of Aflatoxin B1

Targeting histones for degradation in cancer cells as a novel strategy in cancer treatment

Epigenetic Therapies in the Precision Medicine Era

Contact Info

Product

Resources

About