Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of physiology and biochemistry Pub Date : 2024-09-21 DOI:10.1007/s13105-024-01045-8
Idoia Bilbao, Miriam Recalde, Fabrice Daian, José Maria Herranz, María Elizalde, Mercedes Iñarrairaegui, Matteo Canale, Maite G Fernández-Barrena, Andrea Casadei-Gardini, Bruno Sangro, Matías A Ávila, Manuel F Landecho Acha, Carmen Berasain, María Arechederra
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Abstract

DNA methylation is crucial for chromatin structure, transcription regulation and genome stability, defining cellular identity. Aberrant hypermethylation of CpG-rich regions is common in cancer, influencing gene expression. However, the specific contributions of individual epigenetic modifications to tumorigenesis remain under investigation. In hepatocellular carcinoma (HCC), DNA methylation alterations are documented as in other tumor types. We aimed to identify hypermethylated CpGs in HCC, assess their specificity across other tumor types, and investigate their impact on gene expression. To this end, public methylomes from HCC, other liver diseases, and 27 tumor types as well as expression data from TCGA-LIHC and GTEx were analyzed. This study identified 39 CpG sites that were hypermethylated in HCC compared to control liver tissue, and were located within promoter, gene bodies, and intergenic CpG islands. Notably, these CpGs were predominantly unmethylated in healthy liver tissue and other normal tissues. Comparative analysis with 27 other tumors revealed both common and HCC-specific hypermethylated CpGs. Interestingly, the HCC-hypermethylated genes showed minimal expression in the different healthy tissues, with marginal changes in the level of expression in the corresponding tumors. These findings confirm previous evidence on the limited influence of DNA hypermethylation on gene expression regulation in cancer. It also highlights the existence of mechanisms that allow the selection of tissue-specific methylation marks in normally unexpressed genes during carcinogenesis. Overall, our study contributes to demonstrate the complexity of cancer epigenetics, emphasizing the need of better understanding the interplay between DNA methylation, gene expression dynamics, and tumorigenesis.

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对肝细胞癌的 CpG 甲基化进行全面的硅学分析,确定了与基因表达无关的组织和肿瘤类型特异性标记。
DNA 甲基化对染色质结构、转录调控和基因组稳定性至关重要,决定着细胞的特性。富含 CpG 的区域异常高甲基化在癌症中很常见,会影响基因表达。然而,个别表观遗传修饰对肿瘤发生的具体贡献仍在研究中。在肝细胞癌(HCC)中,与其他肿瘤类型一样,DNA甲基化改变也被记录在案。我们的目的是鉴定 HCC 中高甲基化的 CpGs,评估它们在其他肿瘤类型中的特异性,并研究它们对基因表达的影响。为此,我们分析了来自 HCC、其他肝病和 27 种肿瘤类型的公开甲基组以及 TCGA-LIHC 和 GTEx 的表达数据。这项研究发现,与对照肝组织相比,39 个 CpG 位点在 HCC 中发生了高甲基化,这些位点位于启动子、基因体和基因间 CpG 岛。值得注意的是,这些 CpGs 在健康肝组织和其他正常组织中主要是未甲基化的。与其他 27 种肿瘤的比较分析表明,CpGs 既有常见的高甲基化,也有 HCC 特异的高甲基化。有趣的是,HCC 高甲基化基因在不同健康组织中的表达极少,而在相应肿瘤中的表达水平变化不大。这些发现证实了之前关于 DNA 高甲基化对癌症基因表达调控影响有限的证据。研究还强调,在癌变过程中,存在一些机制可以在正常未表达的基因中选择组织特异性甲基化标记。总之,我们的研究有助于证明癌症表观遗传学的复杂性,强调需要更好地理解 DNA 甲基化、基因表达动态和肿瘤发生之间的相互作用。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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