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青少年吸电子烟的表观遗传调控失调:对疾病风险评估的意义

Epigenomic Dysregulation in Youth Vapers: Implications for Disease Risk Assessment

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影响因子:5.3
分区:医学2区 / 生化与分子生物学2区 细胞生物学2区 呼吸系统2区
发表日期:2025 Feb
作者: Stella Tommasi, Luciano Brocchieri, Silvia Tornaletti, Ahmad Besaratinia
DOI: 10.1165/rcmb.2024-0207OC

摘要

尽管青少年吸电子烟的流行仍在持续,但电子烟使用的长期健康影响尚不清楚。我们报道了吸电子烟与吸烟对健康青少年口腔细胞甲基组的影响,比较了非用户、电子烟用户和吸烟者。虽然电子烟用户与吸烟者在差异甲基化区域(DMRs)的数量上存在差异(831对2863个),但它们在DNA甲基化、染色质状态、转录因子结合基序和通路的分布与模式上具有惊人的相似性。电子烟和吸烟者在DMR相关基因上有大量重叠,且共同的基因子富集于转录调控、信号传导、烟草使用障碍和癌症相关通路。特别值得注意的是,在HIC1(癌症高甲基化抑制基因)的启动子区域发现共同的高甲基化DMR,HIC1是一种在吸烟相关癌症中常常被沉默的肿瘤抑制基因。我们的数据支持青少年吸电子烟引起的表观遗传调控失调与疾病风险之间的潜在联系。这些新发现对公共卫生和烟草产品监管具有重要意义。

Abstract

Despite the ongoing epidemic of youth vaping, the long-term health consequences of electronic cigarette use are largely unknown. We report the effects of vaping versus smoking on the oral cell methylome of healthy young vapers and smokers relative to nonusers. Whereas vapers and smokers differ in the number of differentially methylated regions (DMRs) (831 vs. 2,863), they share striking similarities in the distribution and patterns of DNA methylation, chromatin states, transcription factor binding motifs, and pathways. There is substantial overlap in DMR-associated genes between vapers and smokers, with the shared subset of genes enriched for transcriptional regulation, signaling, tobacco use disorders, and cancer-related pathways. Of significance is the identification of a common hypermethylated DMR at the promoter of HIC1 (hypermethylated in cancer 1), a tumor suppressor gene frequently silenced in smoking-related cancers. Our data support a potential link between epigenomic dysregulation in youth vapers and disease risk. These novel findings have significant implications for public health and tobacco product regulation.