Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 335 resistance, spheroid formation, and metastasis in ovarian cancer cells. The overexpression of HOTAIR, facilitated by DNA methylation, thus plays a critical role in ovarian cancer progression and chemoresistance (Braga et al., 2020; Dai et al., 2021). 4.3 Impact on Cancer Progression: Methylation-mediated silencing of tumor suppressor ncRNAs The methylation-mediated silencing of tumor suppressor ncRNAs has profound implications for cancer progression. Tumor suppressor ncRNAs, such as miR-34a, are often silenced by DNA methylation, leading to the loss of their regulatory functions in controlling cell proliferation, apoptosis, and metastasis. The silencing of these ncRNAs removes critical checks on oncogenic pathways, thereby facilitating cancer development and progression. For example, the silencing of miR-34a by promoter hypermethylation results in the upregulation of its target oncogenes, which promote cell cycle progression and inhibit apoptosis. This contributes to the aggressive behavior of ovarian cancer cells and their resistance to conventional therapies. Similarly, the overexpression of HOTAIR, driven by DNA methylation, enhances the metastatic potential of ovarian cancer cells by promoting epithelial-mesenchymal transition (EMT) and anoikis resistance. HOTAIR's interaction with EZH2 and subsequent H3K27 methylation further silences tumor suppressor genes, creating a permissive environment for cancer cell invasion and metastasis (Braga et al., 2020; Dai et al., 2021). DNA methylation plays a pivotal role in regulating the expression and activity of ncRNAs in ovarian cancer. The methylation-mediated silencing of tumor suppressor ncRNAs and the activation of oncogenic lncRNAs like HOTAIR contribute to the complex epigenetic landscape that drives ovarian cancer progression. Understanding these mechanisms provides valuable insights into potential therapeutic targets for combating ovarian cancer. 5 Histone Modifications and Their Impact on ncRNAs in Ovarian Cancer 5.1 Histone acetylation: influence on lncrna regulation and cancer progression Histone acetylation, a key post-translational modification, plays a significant role in the regulation of gene expression by altering chromatin structure and accessibility. This modification is mediated by histone acetyltransferases (HATs) and reversed by histone deacetylases (HDACs). In the context of ovarian cancer, histone acetylation has been shown to influence the expression and function of long non-coding RNAs (lncRNAs), which are crucial regulators of cancer progression. Histone acetylation generally leads to an open chromatin conformation, facilitating transcriptional activation. For instance, the acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) is associated with active transcriptional regions. This modification can enhance the expression of tumor suppressor genes and lncRNAs that inhibit cancer progression. Conversely, the loss of acetylation marks due to the overexpression of HDACs can lead to the repression of these critical genes and lncRNAs, promoting tumorigenesis (Ramaiah et al., 2021). In ovarian cancer, specific lncRNAs have been identified that are regulated by histone acetylation. For example, the lncRNA HOTAIR is known to be upregulated in various cancers, including ovarian cancer, and its expression is influenced by histone acetylation status. HOTAIR can recruit HDACs to specific genomic loci, leading to histone deacetylation and gene silencing, which promotes cancer cell proliferation and metastasis (Forrest and Khalil, 2017; Zhang et al., 2020). Targeting the acetylation status of histones, therefore, represents a potential therapeutic strategy to modulate lncRNA expression and inhibit cancer progression. 5.2 Histone methylation: impact on chromatin accessibility and ncRNA expression Histone methylation, another critical histone modification, involves the addition of methyl groups to lysine or arginine residues on histone proteins. This modification can either activate or repress gene expression, depending on the specific residues that are methylated. Histone methyltransferases (HMTs) and demethylases (HDMTs) are the enzymes responsible for adding and removing these methyl groups, respectively. In ovarian cancer, histone methylation significantly impacts chromatin accessibility and the expression of non-coding RNAs (ncRNAs). For instance, the trimethylation of histone H3 at lysine 27 (H3K27me3) is a
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