Integrative Analysis of DNA Methylation and microRNA Expression Reveals Mechanisms of Racial Heterogeneity in Hepatocellular Carcinoma.
Integrative Analysis of DNA Methylation and microRNA Expression Reveals Mechanisms of Racial Heterogeneity in Hepatocellular Carcinoma.
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DOI：
10.3389/fgene.2021.708326
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发表时间：
2021
影响因子：
3.7
通讯作者：
Ressom HW
中科院分区：
文献类型：
--
作者：
Varghese RS;Barefoot ME;Jain S;Chen Y;Zhang Y;Alley A;Kroemer AH;Tadesse MG;Kumar D;Sherif ZA;Ressom HW
长期以来，表观遗传调控的病理改变被认为是许多癌症的标志，包括肝细胞癌（HCC）。在健康个体中，DNA甲基化与microRNA （miRNA）表达之间的关系保持着良好的平衡；然而，这种和谐的破坏可能有助于癌症的发生或现有癌症的传播。在HCC中，DNA甲基化和microRNA表达之间的平衡及其潜在的干扰可能因种族而异。有新的证据表明，包括DNA甲基化和miRNA表达在内的表观遗传事件与癌症差异有关。在本文中，我们通过DNA甲基化、miRNA和基因表达联合调控的综合分析来评估HCC中种族异质性的表观遗传机制。具体来说，我们通过分析非洲裔美国人（AA）和欧洲裔美国人（EA）肝癌患者的肿瘤和邻近非肿瘤肝脏组织，生成了DNA甲基化、mRNA-seq和miRNA-seq数据。使用混合方差分析，我们确定了细胞嘧啶-磷酸-鸟嘌呤（CpG）位点、mrna和mirna在HCC与邻近非肿瘤组织中以种族特异性的方式显着改变。我们观察到EA的甲基组发生了巨大的变化，差异甲基化和差异表达基因的数量明显多于AA。另一方面，与EA相比，AA中miRNA表达的改变程度更大。通路分析将EA中的表观遗传调控与免疫细胞成熟、炎症和血管重构过程联系起来。相反，细胞增殖、代谢和生长途径在AA中占主导地位，这是表观遗传分析的结果。此外，通过综合分析，我们确定了HCC中具有不同表观遗传调控的显著差异表达基因，这些基因与AA miRNA表达和EA DNA甲基化的变化有关。
Pathologic alterations in epigenetic regulation have long been considered a hallmark of many cancers, including hepatocellular carcinoma (HCC). In a healthy individual, the relationship between DNA methylation and microRNA (miRNA) expression maintains a fine balance; however, disruptions in this harmony can aid in the genesis of cancer or the propagation of existing cancers. The balance between DNA methylation and microRNA expression and its potential disturbance in HCC can vary by race. There is emerging evidence linking epigenetic events including DNA methylation and miRNA expression to cancer disparities. In this paper, we evaluate the epigenetic mechanisms of racial heterogenity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we generated DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent non-tumor liver tissues from African Americans (AA) and European Americans (EA) with HCC. Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are significantly altered in HCC vs. adjacent non-tumor tissue in a race-specific manner. We observed that the methylome was drastically changed in EA with a significantly larger number of differentially methylated and differentially expressed genes than in AA. On the other hand, the miRNA expression was altered to a larger extent in AA than in EA. Pathway analysis functionally linked epigenetic regulation in EA to processes involved in immune cell maturation, inflammation, and vascular remodeling. In contrast, cellular proliferation, metabolism, and growth pathways are found to predominate in AA as a result of this epigenetic analysis. Furthermore, through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA.
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影响因子：
--
作者：
Hashimoto Y;Shiina M;Kato T;Yamamura S;Tanaka Y;Majid S;Saini S;Shahryari V;Kulkarni P;Dasgupta P;Mitsui Y;Sumida M;Deng G;Tabatabai L;Kumar D;Dahiya R
通讯作者：
Dahiya R
1975年至2012年，向国家报告癌症状况的年度报告，其发病率不断增加。
影响因子：
6.2
作者：
Ryerson AB;Eheman CR;Altekruse SF;Ward JW;Jemal A;Sherman RL;Henley SJ;Holtzman D;Lake A;Noone AM;Anderson RN;Ma J;Ly KN;Cronin KA;Penberthy L;Kohler BA
通讯作者：
Kohler BA
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
--
作者：
Shiina, Marisa;Hashimoto, Yutaka;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
3
作者：
Nwaneri AC;McBeth L;Hinds TD Jr
通讯作者：
Hinds TD Jr