Cancer Genetics and Epigenetics 2024, Vol.12, No.2, 106-114 http://medscipublisher.com/index.php/cge 110 3.4 Other epigenetic modification mechanisms In addition to DNA methylation, histone modifications, and non-coding RNA, there are other epigenetic modification mechanisms that together form a complex network regulating gene expression and cellular functions. Glycosylation is a modification process involving the attachment of sugar molecules to proteins or nucleic acids (Yang et al., 2021). Glycosylation modifications are involved in key processes in cancer, such as cell adhesion, signal transduction, and the cell cycle, influencing the proliferation and invasion capabilities of tumor cells. Beyond phosphorylation on histones, many other proteins in cells can be regulated through phosphorylation. Phosphorylation modifications participate in the regulation of various signaling pathways, impacting key processes such as cell survival, proliferation, and apoptosis. Protein acetylation, besides histone acetylation, is also a common epigenetic regulatory mechanism. Acetylation modifications regulate protein stability and function, influencing biological processes such as metabolism, cell cycle, and apoptosis. Ubiquitination modifies other proteins by attaching small ubiquitin proteins. This modification process is involved in crucial processes such as protein degradation, signal transduction, and DNA repair, playing an essential role in maintaining cellular homeostasis and function. Enzymatic modifications, such as those by kinases and phosphatases, regulate protein phosphorylation states and participate in the regulation of multiple cellular signaling pathways. These epigenetic modification mechanisms collectively construct a complex and dense regulatory network, enabling cells to respond to internal and external environmental changes and adjust gene expression and biological processes. In cancer, abnormal changes in these modifications can lead to gene dysregulation, thereby promoting tumor development. 4 The Role of Epigenetics in Cancer Development and Progression 4.1 Abnormal DNA methylation and its relationship with tumors Abnormal DNA methylation is one of the common molecular events in cancer development and progression. This abnormality typically manifests as global hypomethylation and hypermethylation in certain CpG island regions, significantly impacting gene expression and genomic stability. In cancer cells, global hypomethylation is a widespread phenomenon. This hypomethylation state can lead to genomic instability, promoting abnormal variations in key genomic regions, including gene rearrangements and mutations. This instability may be one of the driving forces of cancer development. CpG islands are gene promoter regions rich in CpG dinucleotides. Under normal circumstances, these regions are usually methylated. However, in cancer, abnormal hypermethylation in certain CpG island regions can lead to the silencing of associated genes. These genes are often critical in inhibiting cell proliferation, regulating apoptosis, or participating in DNA repair, and their inactivation may promote cancer development (Casalino and Verde, 2020). DNA repair is a crucial process for maintaining genomic stability, and abnormal methylation of DNA repair genes is closely related to cancer. For example, BRCA1 and BRCA2 are genes involved in DNA repair, and their abnormal methylation can impair DNA repair functions, increasing the risk of hereditary breast and ovarian cancers. Abnormal DNA methylation not only plays a key role in cancer development but may also serve as a biomarker for early cancer events. Measuring DNA methylation levels in blood or tissue can provide clues for early cancer diagnosis and treatment. 4.2 Changes in histone modifications and their association with cancer progression Abnormal changes in histone modifications play a critical role in cancer progression, affecting gene expression, cell cycle regulation, and chromatin structure, thereby driving cancer development and metastasis (Ilango et al., 2020). Histone methylation is an important form of histone modification that influences gene accessibility and transcriptional activity by altering chromatin structure and stability (Figure 3). In cancer, hypermethylation at certain gene loci can lead to the inactivation of tumor suppressor genes, while the hyperactivation of certain oncogenes is also closely associated with abnormal changes in methylation.
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