阴茎鳞状细胞癌中 H19DMR 的低甲基化与 HPV 感染无关。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-01-21 DOI:10.1080/15592294.2024.2305081
Renan da Silva Santos, Daniel Pascoalino Pinheiro, Carlos Gustavo Hirth, Maria Júlia Barbosa Bezerra, Isabelle Joyce de Lima Silva-Fernandes, Francisca Andréa da Silva Oliveira, Maisa Viana de Holanda Barros, Ester Silveira Ramos, Arlindo A Moura, Odorico de Moraes Manoel Filho, Claudia Pessoa, Cristiana Libardi Miranda Furtado
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引用次数: 0

摘要

阴茎鳞状细胞癌(SCC)是一种罕见的侵袭性肿瘤,主要与生活方式和人类乳头瘤病毒(HPV)感染有关。环境诱导的 H19 不同甲基化区(H19DMR)的印记缺失(LOI)与肿瘤发生早期的许多癌症有关,可能与阴茎 SCC 的发病机制有关。我们试图通过亚硫酸氢盐测序(bis-seq)评估阴茎SCC男性患者H19DMR的DNA甲基化模式及其与HPV感染的关系。我们观察到阴茎 SCC H19DMR 的平均甲基化率为 32.2% ± 11.6%,未观察到 p16INK4a+ (p = 0.59) 和高危 HPV+ (p = 0.338) 标记与甲基化水平之间的关联。p16INK4a+或hrHPV+的HPV阳性组(35.4% ± 10%)和这两种标记阴性组(32.4% ± 10.1%)的平均甲基化水平没有变化。由于分析的区域具有 CTCF 蛋白的结合位点,周围 CpG 位点的低甲基化可能会改变其绝缘体功能。此外,多形核细胞的强烈浸润与 H19DMR 的低甲基化呈正相关(p = 0.035)。在此,我们报告了阴茎SCC中H19DMR的低甲基化可能会导致肿瘤的进展和侵袭性,与HPV感染无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection.

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16INK4a+ (p = 0.59) and high-risk HPV+ (p = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16INK4a+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (p = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.

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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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