CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma.
CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma.
复制标题
CXCL12甲基化介导的甲状腺乳头状癌基因表达的表观遗传调控
DOI：
10.1038/srep44033
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发表时间：
2017-03-08
影响因子：
4.6
通讯作者：
Qiao H
中科院分区：
文献类型：
--
作者：
Zhang S;Wang Y;Chen M;Sun L;Han J;Elena VK;Qiao H
甲状腺乳头状癌（PTC）是甲状腺癌中最常见的类型，其发病率正在迅速增长。了解PTC的发病机制对发展有效的诊断方法是必要的。启动子甲基化已被认为有助于在肿瘤发生中观察到的基因表达的改变。我们的RNA-seq数据在PTC中鉴定了1191个差异表达的mRNA和147个差异表达的lncRNA。然后，通过还原型亚硫酸氢盐测序（RRBS）技术检测这些基因的启动子甲基化，并进行综合分析以确定差异甲基化。总共有14个基因（13个mRNA和1个lncRNA），其中甲基化密切参与调节基因表达，被提出作为新的诊断生物标志物。为了深入了解这14个基因之间的关系，基于共表达、共功能和共甲基化数据构建了核心共功能网络。值得注意的是，CXCL 12被确定为网络中与其他基因密切相关的必需基因。这些数据表明，CXCL 12在PTC中的下调可能是由启动子高甲基化引起的。我们的研究是第一个对PTC进行RRBS分析的，并表明CXCL 12可能通过甲基化介导的基因表达的表观遗传调控促进PTC的发展。
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression.
影响因子：
4.4
作者：
Boon K;Tomfohr JK;Bailey NW;Garantziotis S;Li Z;Brass DM;Maruoka S;Hollingsworth JW;Schwartz DA
通讯作者：
Schwartz DA