Abstract
Tumorigenesis is linked to the role of DNA methylation in gene expression regulation. Yet, cancer is a highly heterogeneous disease in which the global pattern of DNA methylation and gene expression, especially across diverse cancers, is not well understood. We investigated DNA methylation status and its association with gene expressions across 12 solid cancer types obtained from The Cancer Genome Atlas. Results showed that global hypermethylation was an important characteristic across all 12 cancer types. Moreover, there were more epigenetically silenced than epigenetically activated genes across the cancers. Further analysis identified epigenetically silenced genes shared in the calcium-signaling pathway across the different cancer types. Reversing the aberrant DNA methylation of genes involved in the calcium-signaling pathway could be an effective strategy for suppressing cancers and developing anti-cancer drugs.
Highlights
Cancer is a complex disease [1, 2], with the dysregulation of genes linked to many tumor features [3, 4]
We investigated DNA methylation status and its association with gene expressions across 12 solid cancer types obtained from The Cancer Genome Atlas
The epigenetically silenced genes were found to be enriched in the calcium-signaling pathway across nine cancer types. These results suggest that various cancers share similarities in DNA methylation, with more epigenetically silenced than epigenetically activated genes identified across cancers, and reversing aberrant DNA methylation of genes involved in the calcium-signaling pathway could be a potential strategy for cancer treatment
Summary
Cancer is a complex disease [1, 2], with the dysregulation of genes linked to many tumor features [3, 4]. Of these cancer-associated genes, oncogenes are usually activated, whereas tumor suppressor genes are inactivated [5]. As the most common epigenetic modification, and as a bridge between gene expression regulation and chromatin architecture [11, 12], DNA methylation is crucial for gene and transposon silencing and imprinting and X chromosome inactivation [13]. Abnormal DNA methylation often occurs in cancers, which regulates the expression of genes, especially those responsible for cell growth, proliferation, differentiation, and apoptosis processes [10, 11, 16]
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