Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 332 cytosine residues in CpG dinucleotides, leading to transcriptional repression. This modification plays a crucial role in the regulation of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). In ovarian cancer, aberrant DNA methylation patterns can significantly impact the expression and function of these ncRNAs. MiRNAs are small ncRNAs that regulate gene expression post-transcriptionally by binding to complementary sequences in target mRNAs, leading to their degradation or translational repression. DNA methylation can silence miRNA genes, thereby preventing their transcription. For instance, hypermethylation of the promoter regions of tumor-suppressive miRNAs can lead to their downregulation, contributing to oncogenesis by allowing the overexpression of their target oncogenes (Anastasiadou et al., 2017; Zhang et al., 2020). Conversely, hypomethylation of oncogenic miRNAs can result in their upregulation, further promoting cancer progression. LncRNAs, which are longer than 200 nucleotides, also undergo regulation by DNA methylation. The methylation status of lncRNA promoters can influence their transcriptional activity. For example, hypermethylation of lncRNA promoters can lead to their silencing, which may disrupt their regulatory roles in gene expression, chromatin remodeling, and other cellular processes (Zhang et al., 2020; Morselli and Dieci, 2022). In ovarian cancer, specific lncRNAs have been identified whose expression is modulated by DNA methylation, affecting tumor growth and metastasis. 3.2 Histone Modifications: Role of Acetylation and Methylation in ncRNA Regulation Histone modifications, including acetylation and methylation, are critical for the regulation of chromatin structure and gene expression. These modifications can either activate or repress transcription, depending on the specific residues modified and the type of modification. In the context of ncRNA regulation, histone modifications play a pivotal role in modulating the expression of miRNAs and lncRNAs. Histone acetylation, typically associated with transcriptional activation, involves the addition of acetyl groups to lysine residues on histone tails. This modification reduces the positive charge on histones, decreasing their affinity for DNA and resulting in a more relaxed chromatin structure that is accessible to transcriptional machinery. Acetylation of histones at miRNA and lncRNA gene promoters can enhance their transcription, thereby influencing their regulatory functions in cancer (Sun et al., 2021; Morselli and Dieci, 2022). Histone methylation, on the other hand, can either activate or repress transcription depending on the specific lysine or arginine residues methylated. For instance, trimethylation of histone H3 at lysine 4 (H3K4me3) is associated with active transcription, while trimethylation at lysine 27 (H3K27me3) is linked to transcriptional repression. In ovarian cancer, dysregulation of histone methylation patterns can alter the expression of ncRNAs, contributing to tumorigenesis. For example, the repression of tumor-suppressive miRNAs and lncRNAs through H3K27me3 can promote cancer cell proliferation and survival (Sun et al., 2021). 3.3 Chromatin remodeling: how chromatin structure impacts ncRNA expression Chromatin remodeling refers to the dynamic modification of chromatin architecture to allow access to the genomic DNA for transcription, replication, and repair. This process is mediated by chromatin remodeling complexes that reposition, eject, or restructure nucleosomes. The regulation of ncRNA expression by chromatin remodeling is a critical aspect of epigenetic control in ovarian cancer. Chromatin remodeling complexes, such as SWI/SNF, can alter the positioning of nucleosomes, thereby modulating the accessibility of ncRNA gene promoters to transcription factors and RNA polymerases. In ovarian cancer, mutations or alterations in the expression of chromatin remodeling components can lead to aberrant ncRNA expression. For instance, the loss of function of SWI/SNF components can result in the repression of tumor-suppressive ncRNAs, contributing to cancer progression (Anastasiadou et al., 2017; Morselli and Dieci, 2022). Additionally, the three-dimensional organization of the genome, influenced by chromatin remodeling, plays a significant role in ncRNA regulation. The formation of chromatin loops and topologically associating domains
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