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Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression.

ABSTRACT: 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.

SUBMITTER: Wu J

PROVIDER: S-EPMC6369581 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression.

Wu Jun J Gu Yunzhao Y Xiao Yawen Y Xia Chao C Li Hua H Kang Yani Y Sun Jielin J Shao Zhifeng Z Lin Zongli Z Zhao Xiaodong X

Frontiers in genetics 20190204

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 pa ...[more]

PMID: 30778372

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Project description:Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk.The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development.Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression.Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (? = -0.0014; 95% CI: -0.0023, -0.0005, p = 0.002), stronger in males (? = -0.0024; 95% CI: -0.0038, -0.0009, p = 0.003) than in females (? = -0.0009; 95% CI: -0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (? = -0.0013; 95% CI: -0.0023, -0.0003, p = 0.01) DMR methylation, but primarily in females, (? = -0.0017; 95% CI: -0.0029, -0.0006, p = 0.005) rather than in males, (? = -0.0004; 95% CI: -0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (? = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months.Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood.Li Y, Xie C, Murphy SK, Skaar D, Nye M, Vidal AC, Cecil KM, Dietrich KN, Puga A, Jirtle RL, Hoyo C. 2016. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood. Environ Health Perspect 124:666-673; http://dx.doi.org/10.1289/ehp.1408577.

Dataset Information

Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression.

Publications

Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression.

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