Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression
Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression
复制标题
胃癌进展过程中 DNA 甲基化相关基因调控网络的表征
DOI：
10.3389/fgene.2018.00711
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发表时间：
2019-02-04
影响因子：
3.7
通讯作者：
Zhao, Xiaodong
中科院分区：
文献类型：
--
作者：
Wu, Jun;Gu, Yunzhao;Zhao, Xiaodong
DNA甲基化通过调节癌基因激活和肿瘤抑制基因沉默，在肿瘤发生中起着至关重要的作用。虽然被广泛分析，但DNA甲基化在基因调控网络中的含义却很少被描述。为了解决这个问题，在本研究中，我们对不同阶段胃癌的DNA甲基化模式的改变和基因调控网络拓扑的动态进行了综合分析。我们发现，不同阶段的DNA甲基化模式总体上是保守的，而一些显著差异的甲基化基因仅在胃癌的早期阶段观察到。DNA甲基化和网络拓扑改变的综合分析得出了几个已报道的参与胃癌进展的基因，如IGF2、ERBB2、GSTP1、MYH11、TMEM59和SST。最后，我们证明抑制SST促进细胞增殖，这表明DNA甲基化相关的SST抑制可能有助于胃癌的进展。综上所述，我们的研究表明DNA甲基化相关的调控网络分析可以用于识别癌症相关基因。该策略可以促进对癌症生物学中基因调控网络的理解，并为在系统水平上研究DNA甲基化提供新的见解。
DNA methylation plays a critical role in tumorigenesis through regulating oncogene activation and tumor suppressor gene silencing. Although extensively analyzed, the implication of DNA methylation in gene regulatory network is less characterized. To address this issue, in this study we performed an integrative analysis on the alteration of DNA methylation patterns and the dynamics of gene regulatory network topology across distinct stages of stomach cancer. We found the global DNA methylation patterns in different stages are generally conserved, whereas some significantly differentially methylated genes were exclusively observed in the early stage of stomach cancer. Integrative analysis of DNA methylation and network topology alteration yielded several genes which have been reported to be involved in the progression of stomach cancer, such as IGF2, ERBB2, GSTP1, MYH11, TMEM59, and SST. Finally, we demonstrated that inhibition of SST promotes cell proliferation, suggesting that DNA methylation-associated SST suppression possibly contributes to the gastric cancer progression. Taken together, our study suggests the DNA methylation-associated regulatory network analysis could be used for identifying cancer-related genes. This strategy can facilitate the understanding of gene regulatory network in cancer biology and provide a new insight into the study of DNA methylation at system level.