Abstract:Atherosclerosis (AS), the most common underlying pathology for coronary artery disease, is a chronic inflammatory, proliferative disease in large- and medium-sized arteries. The vascular endothelium is important for maintaining vascular health. Endothelial dysfunction is a critical early event leading to AS, which is a major risk factor for stroke and myocardial infarction. Accumulating evidence has suggested the critical roles of histone deacetylases (HDACs) in regulating vascular cell homeostasis and AS. The… Show more
“…In the epigenetic research of tumor occurrence and development, it has gradually attracted academic wide attention in the world. Most of the current research focuses on the chemical modification and structural modification of the existing antitumor drugs with HDACs inhibitory activity to enhance the therapeutic effect of the drug and alleviate the toxic and side effects (Chen et al,2020). There are currently few antitumor drugs designed to act on specific targets and specific pathways.…”
Background The occurrence and development of tumors are closely related to histone deacetylases (HDACs). However,the overall biology and prognosis are still unknown in glioma. In the present study,we comprehensively explored the biology function and prognosis of eleven HDAC genes in glioma,which may contribute the more understanding of molecular mechanisms and potential therapeutic targets for glioma patients.
Methods We systematically described the expression files, molecular subtypes, prognostic value,immune filtration and tumor microenvironment and gene alteration,function and pathways enrichment,and drug sensitivity using TCGA and CGGA datasets. We developed and validated the prognostic model based on HDACs genes in glioma using LASSO,univariate, and multivariate cox regression. Receiver operating characteristic analyses were used for model evaluating. We also validated the expressions of HDACs genes included in the model in non-tumor and glioma tissues samples.
Results Glioma patients can be divided into two subclasses based on eleven HDAC genes, and patients from two subclasses had markedly different survival outcomes. Then, using six HDAC genes (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), we established a prognostic model in glioma patients, and this prognostic model was well validated in an independent cohort population. Furthermore, the calculated risk score from six HDACA genes expression was suggested to be an independent prognostic factor, which can predict the five-year overall survival of glioma patients well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low- risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, we identified several small molecular compounds that could be favorable for glioma patients treatment. And finally, the expression levels of HDAC genes from prognostic model were validated in glioma and non-tumor tissues samples.
Conclusion Our results revealed the clinical utility and potential molecular mechanisms of HDAC genes in glioma. Model based on six HDAC genes can predict the overall survival of glioma patients well, which can be served as potential therapeutic targets.
“…In the epigenetic research of tumor occurrence and development, it has gradually attracted academic wide attention in the world. Most of the current research focuses on the chemical modification and structural modification of the existing antitumor drugs with HDACs inhibitory activity to enhance the therapeutic effect of the drug and alleviate the toxic and side effects (Chen et al,2020). There are currently few antitumor drugs designed to act on specific targets and specific pathways.…”
Background The occurrence and development of tumors are closely related to histone deacetylases (HDACs). However,the overall biology and prognosis are still unknown in glioma. In the present study,we comprehensively explored the biology function and prognosis of eleven HDAC genes in glioma,which may contribute the more understanding of molecular mechanisms and potential therapeutic targets for glioma patients.
Methods We systematically described the expression files, molecular subtypes, prognostic value,immune filtration and tumor microenvironment and gene alteration,function and pathways enrichment,and drug sensitivity using TCGA and CGGA datasets. We developed and validated the prognostic model based on HDACs genes in glioma using LASSO,univariate, and multivariate cox regression. Receiver operating characteristic analyses were used for model evaluating. We also validated the expressions of HDACs genes included in the model in non-tumor and glioma tissues samples.
Results Glioma patients can be divided into two subclasses based on eleven HDAC genes, and patients from two subclasses had markedly different survival outcomes. Then, using six HDAC genes (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), we established a prognostic model in glioma patients, and this prognostic model was well validated in an independent cohort population. Furthermore, the calculated risk score from six HDACA genes expression was suggested to be an independent prognostic factor, which can predict the five-year overall survival of glioma patients well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low- risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, we identified several small molecular compounds that could be favorable for glioma patients treatment. And finally, the expression levels of HDAC genes from prognostic model were validated in glioma and non-tumor tissues samples.
Conclusion Our results revealed the clinical utility and potential molecular mechanisms of HDAC genes in glioma. Model based on six HDAC genes can predict the overall survival of glioma patients well, which can be served as potential therapeutic targets.
Histone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.
“…Histone acetylation, mediating via HATs, is defined as adding positive acetyl groups to amino acid residues of histones, which reduces the combination between histone protein and DNA and further activates gene expression. Histone deacetylases, mediating via HDACs, refers to the removal the acetylated residues at lysine and further inhibits gene expression ( Chen et al, 2020 ). Recently, various studies have confirmed the key role HATs and HDACs played in the pathology of atherosclerosis.…”
Section: Epigenetic Regulation Of Atherosclerosismentioning
Atherosclerosis, characterized by atherosclerotic plaques, is a complex pathological process that involves different cell types and can be seen as a chronic inflammatory disease. In the advanced stage, the ruptured atherosclerotic plaque can induce deadly accidents including ischemic stroke and myocardial infarction. Epigenetics regulation, including DNA methylation, histone modification, and non-coding RNA modification. maintains cellular identity via affecting the cellular transcriptome. The epigenetic modification process, mediating by epigenetic enzymes, is dynamic under various stimuli, which can be reversely altered. Recently, numerous studies have evidenced the close relationship between atherosclerosis and epigenetic regulations in atherosclerosis, providing us with a novel perspective in researching mechanisms and finding novel therapeutic targets of this serious disease. Here, we critically review the recent discoveries between epigenetic regulation mechanisms in atherosclerosis.
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