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恶性涎腺肿瘤的染色质乙酰化减少与增殖增强相关。

Reduced chromatin acetylation of malignant salivary gland tumors correlates with enhanced proliferation.

机构信息

Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Department of Experimental Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

J Oral Pathol Med. 2017 Oct;46(9):792-797. doi: 10.1111/jop.12557. Epub 2017 Apr 9.

Abstract

BACKGROUND

Epigenetic changes refer to any heritable modification in gene expression independent of alterations in the DNA sequence. Currently, it is well established that epigenetics represents a crucial player for tumor development. Nevertheless, the epigenetic mechanisms involved in the development and progression of salivary gland tumors (SGTs) remain poorly understood.

METHODS

In this study, we analyzed the pattern of acetyl-histone H3 (lys9) expression in benign and malignant SGTs and further correlate our results with tumors' proliferative activity and clinical outcomes. We assembled tissue microarrays (TMAs) of 84 cases of SGTs and analyzed for acetyl-histone H3 (lys9) and Ki-67 using immunohistochemistry. The study comprised 42 benign and 42 malignant SGTs.

RESULTS

All cases included in this study were positive to acetyl-H3 (lys9). We observed that malignant SGTs were hypoacetylated compared with benign (P = 0.04). Moreover, acetyl-H3 (lys9) expression was inversely correlated with Ki67 (**P = 0.02).

CONCLUSION

This study provides the first insight regarding histone modifications in SGTs. Our results suggest that epigenetic mechanism, particularly hypoacetylation of histone H3 (lys9), might play a role in the behavior of salivary gland tumors. Also, our findings suggest that interfering with the acetylation pattern of tumor histones represents a potential novel therapeutic strategy for the treatment of SGTs.

摘要

背景

表观遗传变化是指基因表达的任何可遗传修饰,而与 DNA 序列的改变无关。目前,人们已经充分认识到表观遗传在肿瘤发生中起着至关重要的作用。然而,唾液腺肿瘤(SGT)发生和进展中涉及的表观遗传机制仍知之甚少。

方法

在这项研究中,我们分析了良性和恶性 SGT 中乙酰组蛋白 H3(赖氨酸 9)表达的模式,并进一步将我们的结果与肿瘤的增殖活性和临床结果相关联。我们组装了 84 例 SGT 的组织微阵列(TMA),并使用免疫组织化学法分析乙酰组蛋白 H3(赖氨酸 9)和 Ki-67。研究包括 42 例良性和 42 例恶性 SGT。

结果

本研究中包括的所有病例均对乙酰-H3(赖氨酸 9)呈阳性。我们观察到恶性 SGT 的乙酰化程度低于良性 SGT(P=0.04)。此外,乙酰化-H3(赖氨酸 9)的表达与 Ki67 呈负相关(P=0.02)。

结论

本研究首次提供了关于 SGT 组蛋白修饰的见解。我们的研究结果表明,表观遗传机制,特别是组蛋白 H3(赖氨酸 9)的低乙酰化,可能在唾液腺肿瘤的行为中发挥作用。此外,我们的研究结果表明,干扰肿瘤组蛋白的乙酰化模式可能是治疗 SGT 的一种潜在的新治疗策略。

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