Hong Juyeon, Rhee Je-Keun
Department of Bioinformatics & Life Science, Soongsil University, Seoul 06978, Korea.
Biology (Basel). 2022 Sep 23;11(10):1388. doi: 10.3390/biology11101388.
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.
癌症相关基因的异常表达可导致结直肠癌（CRC）的发生，而DNA甲基化是异常表达的原因之一。尽管已经进行了许多研究来揭示DNA甲基化如何影响转录调控，但其调节基因表达的方式以及显著影响DNA甲基化介导的基因调控的区域仍不清楚。在本研究中，我们调查了特定基因组区域的DNA甲基化如何影响基因表达。基于DNA甲基化构建了几个用于基因表达预测的回归模型。在这些模型中，选择性能最佳的弹性网络（ElasticNet）进行进一步分析。转录起始位点（TSS）附近的DNA甲基化，特别是TSS上游2 kb至下游7 kb的区域，对基因表达具有重要的调控作用。此外，对受甲基化影响且与生存相关的基因进行了汇编，发现它们主要富集在免疫相关途径中。本研究调查了甲基化变化可影响基因表达的基因组区域。此外，本研究提出，由于DNA甲基化导致的异常表达基因可通过免疫系统导致CRC发病机制。
