International Journal of Molecular Medical Science, 2024, Vol.14, No.4, 227-238 http://medscipublisher.com/index.php/ijmms 231 5.2.2 Oncogenes While the hypermethylation of tumor suppressor genes is a common feature, the role of DNA methylation in the regulation of oncogenes is more complex. Some oncogenes may be activated through hypomethylation, leading to their overexpression and promoting cancer cell proliferation and survival (Moarii et al., 2015). However, the precise mechanisms and the extent to which DNA methylation directly influences oncogene activation in colon cancer require further investigation (Qu et al., 2013). 5.3 DNA methylation and cancer hallmarks 5.3.1 Cell proliferation DNA methylation plays a crucial role in regulating cell proliferation in colon cancer. The hypermethylation and subsequent silencing of tumor suppressor genes such as CDKN2A lead to unchecked cell cycle progression and increased cell proliferation (Pfeifer, 2018). Additionally, hypomethylation of oncogenes can further drive the proliferative capacity of cancer cells (Moarii et al., 2015). 5.3.2 Apoptosis The evasion of apoptosis is a key hallmark of cancer, and DNA methylation contributes to this process in colon cancer. Hypermethylation of pro-apoptotic genes, such as BAX and APAF1, results in their silencing, thereby allowing cancer cells to evade programmed cell death (Pfeifer, 2018). This epigenetic alteration supports the survival and accumulation of malignant cells (Jung et al., 2020). 5.3.3 Angiogenesis Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. DNA methylation can influence angiogenesis by regulating the expression of angiogenic factors. For example, the hypermethylation of anti-angiogenic genes can lead to their downregulation, promoting a pro-angiogenic environment that supports tumor vascularization (Sharma et al., 2010; Nebbioso et al., 2018). 5.3.4 Metastasis Metastasis, the spread of cancer cells to distant organs, is a major cause of cancer-related mortality. DNA methylation changes are implicated in the metastatic process of colon cancer. Hypermethylation of genes involved in cell adhesion and extracellular matrix remodeling, such as E-cadherin, can facilitate the detachment and invasion of cancer cells (Pfeifer, 2018). Additionally, the methylation status of metastasis-related genes can serve as biomarkers for predicting metastatic potential and patient prognosis (Jung et al., 2020; Davalos and Esteller, 2022). DNA methylation is a critical epigenetic modification that influences various aspects of colon cancer biology, from gene-specific changes to global methylation patterns, and plays a significant role in the hallmarks of cancer. Understanding these methylation changes provides valuable insights into the mechanisms of colon cancer and offers potential avenues for therapeutic intervention and biomarker development. 6 Techniques for Studying DNA Methylation The study of DNA methylation is essential for understanding gene regulation and its implications in various biological processes and diseases. Techniques such as bisulfite sequencing, methylation-specific PCR, pyrosequencing, high-throughput methylation arrays, and emerging technologies like single-cell methylome analysis offer diverse and complementary approaches for analyzing DNA methylation. Each method has its strengths and limitations, and the choice of technique depends on the specific research question and available resources. By leveraging these techniques, researchers can gain a comprehensive understanding of DNA methylation patterns and their functional significance. Bisulfite sequencing is considered the gold standard for DNA methylation analysis. This technique involves treating DNA with bisulfite, which converts unmethylated cytosines to uracil while leaving methylated cytosines unchanged. The treated DNA is then sequenced to determine the methylation status at single-base resolution. High-throughput bisulfite sequencing can be applied either genome-wide or targeted to specific loci, providing
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