The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy

Yang, Yunkai; Zhang, Min; Wang, Yan

doi:10.1016/j.jncc.2022.09.002

Cited by 44 publications

(17 citation statements)

References 233 publications

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“…The methylation of H3K4 and H3K79 histones via COMPASS and DOT1L enzymes, respectively, presupposes prior H2B ubiquitination [ 74 ]. The interplay between distinct histone modifications or the crosstalk between enzymes that modify histones requires further elucidation [ 75 ]. The observation that the expression of ubiquitinated H2B is notably reduced in gastric cancer cases suggests a potential therapeutic role for the histone-ubiquitination process [ 71 ].…”

Section: Epigenetics Background (Dna Methylation Histone Modification...mentioning

confidence: 99%

Gastric Cancer in the Era of Epigenetics

Christodoulidis,

Koumarelas,

Kouliou

et al. 2024

IJMS

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Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein–Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor’s metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance.

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Section: Epigenetics Background (Dna Methylation Histone Modification...mentioning

confidence: 99%

Gastric Cancer in the Era of Epigenetics

Christodoulidis,

Koumarelas,

Kouliou

et al. 2024

IJMS

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“…During tumorigenesis, cells gradually lose their differentiated phenotype and acquire stem-cell features [20][21][22]. Indeed, the alteration in HME expression and dysregulation of a wide genome distribution of histone modifications and DNA methylation have been observed in several cancer types [23][24][25]. For instance, a significant decrease in H3K79me3 levels has been described in lung, bladder, and skin tumors, when compared with normal tissues [26], and low H3K9me2/3 and H3K4me1 levels have been reported in localized prostate cancer with respect to normal tissue [27].…”

Section: Of 16mentioning

confidence: 99%

In Vivo Identification of H3K9me2/H3K79me3 as an Epigenetic Barrier to Carcinogenesis

Piro,

Gasperi,

De Stefano

et al. 2023

IJMS

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The highly dynamic nature of chromatin’s structure, due to the epigenetic alterations of histones and DNA, controls cellular plasticity and allows the rewiring of the epigenetic landscape required for either cell differentiation or cell (re)programming. To dissect the epigenetic switch enabling the programming of a cancer cell, we carried out wide genome analysis of Histone 3 (H3) modifications during osteogenic differentiation of SH-SY5Y neuroblastoma cells. The most significant modifications concerned H3K27me2/3, H3K9me2, H3K79me1/2, and H3K4me1 that specify the process of healthy adult stem cell differentiation. Next, we translated these findings in vivo, assessing H3K27, H3K9, and H3K79 methylation states in biopsies derived from patients affected by basalioma, head and neck carcinoma, and bladder tumors. Interestingly, we found a drastic decrease in H3K9me2 and H3K79me3 in cancer specimens with respect to their healthy counterparts and also a positive correlation between these two epigenetic flags in all three tumors. Therefore, we suggest that elevated global levels of H3K9me2 and H3K79me3, present in normal differentiated cells but lost in malignancy, may reflect an important epigenetic barrier to tumorigenesis. This suggestion is further corroborated, at least in part, by the deranged expression of the most relevant H3 modifier enzymes, as revealed by bioinformatic analysis. Overall, our study indicates that the simultaneous occurrence of H3K9me2 and H3K79me3 is fundamental to ensure the integrity of differentiated tissues and, thus, their combined evaluation may represent a novel diagnostic marker and potential therapeutic target.

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“…Epigenetics such as histone modification could regulate the expression of oncogenes and tumor suppressors. 22 Therefore, it is important to investigate epigenetic mechanisms that regulate P450, CD24 and HER-2/neu expression in endometrial cancer. This study has several limitations.…”

Section: Correlation Of the Expression Of Aromatase P450 Cd24 And Her...mentioning

confidence: 99%

Expression and clinical significance of HER2/neu, aromatase P450 and adhesion molecule CD24 in endometrial cancer

Guan¹,

Wang

Cheng

et al. 2023

Eur J Histochem

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This study aimed at exploring the expression and clinical significance of aromatase P450, adhesion molecule CD24 and HER2/neu in endometrial cancer. The expression of aromatase P450, adhesion molecule CD24 and HER2/neu was detected by immunohistochemistry in 15 cases of endometrial hyperplasia group, 50 cases of endometrial adenocarcinoma and 3 cases of uterine papillary adenocarcinoma, with 15 cases of normal endometrium as control group. We detected no expression of aromatase P450, adhesion molecule CD24 or HER2/neu in control group. Aromatase P450 positive expression rate was 66.7% in endometrial hyperplasia group and 70.3% in endometrial carcinoma group, without significant difference (p>0.05). There was no significant difference (p>0.05) in the positive expression rate of aromatase P450 between different myometrial invasion groups of endometrial adenocarcinomas. CD24 positive expression rate was 40.0% in endometrial hyperplasia group and 79.6% in endometrial carcinoma group, with significant difference (p<0.05). HER2/neu positive expression rate was 26.7% in the endometrial hyperplasia group and 57% in endometrial carcinoma group, with significant difference (p<0.05). In conclusion, aromatase P450 may be one factor associated with endometrial cancer cell proliferation, while CD24 and HER2/neu may be important factors associated with the invasion and metastasis of endometrial cancer.

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The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy

Cited by 44 publications

References 233 publications

Gastric Cancer in the Era of Epigenetics

Gastric Cancer in the Era of Epigenetics

In Vivo Identification of H3K9me2/H3K79me3 as an Epigenetic Barrier to Carcinogenesis

Expression and clinical significance of HER2/neu, aromatase P450 and adhesion molecule CD24 in endometrial cancer

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