Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 329-345 http://medscipublisher.com/index.php/cge 334 Figure 2 Epigenetic regulation by lncRNAs (Adopted from Zhang et al., 2010) Image caption: (A) LncRNA HOX transcript antisense intergenic RNA (HOTAIR) regulates HOXD cluster genes via the recruitment of the polycomb repressive complex 2 (PRC2) silencing complex to execute gene silencing by histone H3 lysine 27 tri-methylation (H3K27me3). (B) LncRNA FGFR2-AS recruits the PRC2 complex and histone demethylase KDM2a to the FGFR2 locus, generating a splicing-specific chromatin signature. (C) LncRNA HOXD antisense growth-associated long non-coding RNA (HOXD-AS1) recruits the WD repeat domain 5 (WDR5)-mixed-lineage leukemia (MLL) complex and mediates histone H3 lysine 4 tri-methylation (H3K4me3) to directly regulate the expression of target genes. (D) Divergent lncRNA of FZD6 (LncFZD6) recruits the BRG1-embedded SWI/SNF complex to the FZD6 promoter and drives FZD6 transcription (Adopted from Zhang et al., 2010) 4.2 Examples of Methylation-altered ncRNAs: miR-34a, lncRNA HOTAIR, and their links to cancer development One of the well-studied examples of methylation-altered ncRNAs in ovarian cancer is miR-34a. miR-34a acts as a tumor suppressor and is often silenced by promoter hypermethylation in various cancers, including ovarian cancer. The silencing of miR-34a leads to the deregulation of its target genes, which are involved in cell cycle control, apoptosis, and metastasis. The loss of miR-34a expression due to DNA methylation contributes to the unchecked proliferation and survival of cancer cells, thereby promoting tumorigenesis (Zhang et al., 2020). Another significant ncRNA affected by DNA methylation is the lncRNA HOTAIR. HOTAIR is known to be overexpressed in ovarian cancer, and its expression is regulated by epigenetic modifications, including DNA methylation. HOTAIR recruits the polycomb repressive complex 2 (PRC2) and enhances H3K27 methylation, leading to the silencing of tumor suppressor genes. This epigenetic regulation by HOTAIR promotes anoikis
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