Comprehensive Characterization of HATs and HDACs in Human Cancers Reveals Their Role in Immune Checkpoint Blockade.

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2023049102

Rong Sun, Zike Chen, Xuanhao Qu, Jie Zhang, Lehan Liu, Zhuheng Zhong, Weibing Zhang, Yihui Fan

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引用次数: 0

Abstract

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

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人类癌症中hat和hdac的综合特征揭示了它们在免疫检查点阻断中的作用。

组蛋白乙酰化由组蛋白乙酰转移酶（HATs）和组蛋白脱乙酰酶（HDACs）两个相互拮抗的酶家族控制，作为控制转录的主要表观遗传学机制之一，其异常调节与癌症的各个方面有关。然而，对癌症中HDAC和HAT的全面了解仍然缺乏。基于下一代序列数据对33种癌症类型进行系统分析，揭示了不同癌症类型的HDAC和HAT的异质表达模式。特别是HDAC10和HDAC6在大多数癌症中表现出显著的下调。全癌组织的主成分分析（PCA）显示，正常组织和癌旁正常组织的HDAC和HAT存在显著差异。在多种类型的癌症中，HDAC和HAT的异常表达部分是由于CNV和DNA甲基化。HDACs和HATs的预后显著性（AUC达到0.736）表明KIRC中存在五个基因特征，包括KAT2A、HAT1、KAT5、CREBBP和SIRT1。对NCI-60药物数据库的分析表明，几种药物的细胞毒性作用与HDAC和HAT表达失调有关。免疫浸润和免疫治疗分析表明，KAT2B和HDAC9与免疫浸润和治疗有关。我们的分析提供了对泛癌中HDAC和HAT的调节和影响的全面理解。这些发现为未来癌症发展和治疗中潜在的个体HDAC和HAT的生物学研究提供了新的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.