Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 336 repressive mark associated with gene silencing. The enzyme EZH2, a component of the Polycomb Repressive Complex 2 (PRC2), catalyzes this modification and is often overexpressed in ovarian cancer, leading to the repression of tumor suppressor genes and ncRNAs (Chatterjee et al., 2019; Sun et al., 2021). Conversely, the methylation of histone H3 at lysine 4 (H3K4me3) is an activating mark associated with transcriptional initiation. This modification can enhance the expression of oncogenic lncRNAs, contributing to cancer progression. For example, the lncRNA MALAT1 is upregulated in ovarian cancer and is associated with H3K4me3 marks at its promoter region, facilitating its transcription and promoting tumor growth and metastasis (Forrest and Khalil, 2017; Zhang et al., 2020). 5.3 Case studies: histone-modified lncRNAs influencing tumor behavior Several case studies highlight the role of histone-modified lncRNAs in influencing tumor behavior in ovarian cancer. One notable example is the lncRNA HOTAIR, which is regulated by both histone acetylation and methylation. HOTAIR can recruit PRC2 to specific genomic loci, leading to H3K27me3-mediated gene silencing. This epigenetic regulation by HOTAIR promotes cancer cell proliferation, invasion, and metastasis (Forrest and Khalil, 2017; Chatterjee et al., 2019; Zhang et al., 2020). Another example is the lncRNA ANRIL, which is associated with the repression of tumor suppressor genes through histone modifications. ANRIL interacts with PRC1 and PRC2, leading to the deposition of repressive histone marks such as H3K27me3 and H2AK119ub1 at the INK4/ARF locus, resulting in the silencing of these critical tumor suppressor genes and promoting cancer progression (Forrest and Khalil, 2017; Zhang et al., 2020). Furthermore, the lncRNA MEG3 has been shown to be downregulated in ovarian cancer due to histone deacetylation. MEG3 acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. The loss of histone acetylation marks at the MEG3 promoter region leads to its silencing, contributing to tumorigenesis (Forrest and Khalil, 2017; Zhang et al., 2020; Ramaiah et al., 2021). In conclusion, histone modifications such as acetylation and methylation play crucial roles in regulating the expression and function of lncRNAs in ovarian cancer. These modifications can either promote or inhibit cancer progression by altering chromatin accessibility and gene expression. Understanding the interplay between histone modifications and lncRNAs provides valuable insights into the epigenetic regulation of cancer and offers potential therapeutic targets for the treatment of ovarian cancer. 6 Chromatin Remodeling and Its Effect on ncRNA Regulation in Ovarian Cancer 6.1 Chromatin state alterations: impact on ncRNA gene accessibility and transcription Chromatin state alterations play a crucial role in the regulation of non-coding RNA (ncRNA) gene accessibility and transcription in ovarian cancer. The dynamic nature of chromatin, which involves modifications such as methylation and acetylation of histones, can either promote or inhibit the transcription of ncRNA genes. For instance, the heterogeneity of chromatin states within ncRNA multigene families can significantly influence their transcriptional activity and 3D genome organization, thereby affecting gene expression patterns critical for cancer progression (Morselli and Dieci, 2022). In ovarian cancer, specific chromatin modifications can lead to the activation or repression of ncRNA genes, which in turn modulate the expression of oncogenes or tumor suppressor genes. For example, the deregulation of DNA methylation and histone modifications has been shown to alter the expression of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contributing to the malignant phenotype of cancer cells (Forrest and Khalil, 2017; Farooqi et al., 2020). These epigenetic changes can result in the aberrant expression of ncRNAs, which may further influence chromatin structure and function, creating a feedback loop that perpetuates cancer progression. 6.2 Role of chromatin remodeling complexes: effect on ncRNA functions in cancer Chromatin remodeling complexes are essential for the regulation of ncRNA functions in cancer. These complexes, such as the SWI/SNF and polycomb repressive complexes, play a pivotal role in nucleosome assembly and
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