Genomic Effect of DNA Methylation on Gene Expression in Colorectal Cancer
Juyeon Hong,Je-Keun Rhee +1 more
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This study investigated genomic regions in which methylation changes can affect gene expression and proposed that aberrantly expressed genes due to DNA methylation can lead to CRC pathogenesis by the immune system.Abstract:
Simple Summary Abnormal DNA methylation is known to regulate gene expression, and its features have been frequently observed in colorectal cancer (CRC) patients. In addition, alterations in DNA methylation can be proposed as biomarkers for cancer prognosis, as they occur in the early stage of carcinogenesis. Although numerous studies have attempted to shed light on the impacts of DNA methylation on gene expression, it is still unclear which specific regions regulate gene expression and how they are associated with patient survival. In this study, we elucidated the intricate relationship between DNA methylation and gene expression. Furthermore, we found genes that were influenced by DNA methylation and were associated with survival; these genes were mainly enriched in immune-related pathways. Abstract The aberrant expression of cancer-related genes can lead to colorectal cancer (CRC) carcinogenesis, and DNA methylation is one of the causes of abnormal expression. Although many studies have been conducted to reveal how DNA methylation affects transcription regulation, the ways in which it modulates gene expression and the regions that significantly affect DNA methylation-mediated gene regulation remain unclear. In this study, we investigated how DNA methylation in specific genomic areas can influence gene expression. Several regression models were constructed for gene expression prediction based on DNA methylation. Among these models, ElasticNet, which had the best performance, was chosen for further analysis. DNA methylation near transcription start sites (TSS), especially from 2 kb upstream to 7 kb downstream of TSS, had an essential regulatory role in gene expression. Moreover, methylation-affected and survival-associated genes were compiled and found to be mainly enriched in immune-related pathways. This study investigated genomic regions in which methylation changes can affect gene expression. In addition, this study proposed that aberrantly expressed genes due to DNA methylation can lead to CRC pathogenesis by the immune system.read more
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