Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 358-367 http://medscipublisher.com/index.php/cge 360 2.3 Functional roles in cellular processes LncRNAs and miRNAs are involved in a wide range of cellular processes. LncRNAs can modulate gene expression by acting as molecular scaffolds, guides, decoys, or sponges, thereby influencing chromatin structure, transcription, and post-transcriptional events. They play roles in cellular differentiation, proliferation, migration, and apoptosis, and are implicated in various diseases, including cancer (Ballantyne et al., 2016; Chen et al., 2018; Tang et al., 2019). MiRNAs, on the other hand, primarily function as post-transcriptional regulators of gene expression. They are involved in critical biological processes such as development, differentiation, proliferation, and apoptosis. Dysregulation of miRNAs is associated with various diseases, including cancer, where they can act as oncogenes or tumor suppressors (O'Brien et al., 2018; Tam et al., 2019; Annese et al., 2020). In summary, both lncRNAs and miRNAs are essential regulators of gene expression, with distinct but sometimes overlapping roles in cellular processes. Their intricate regulatory networks and interactions are crucial for maintaining cellular homeostasis and responding to environmental changes (Ballantyne et al., 2016; Chen et al., 2018; Tang et al., 2019). 3 lncRNAs in Colon Cancer Progression 3.1 Key lncRNAs implicated in colon cancer Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the progression of colorectal cancer (CRC). Among the numerous lncRNAs identified, several have been extensively studied for their roles in CRC. Notable examples include HIF1A-AS2, TTN-AS1, and FEZF1-AS1. HIF1A-AS2: This lncRNA has been shown to promote CRC progression by acting as a competing endogenous RNA (ceRNA) for miR-129-5p, thereby regulating the expression of DNMT3A. The upregulation of HIF1A-AS2 enhances cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in CRC cells (Lin et al., 2018). TTN-AS1: TTN-AS1 facilitates CRC progression by sponging miR-376a-3p, which leads to the upregulation of KLF15. This interaction promotes cell proliferation, invasion, and reduces apoptosis in CRC cells (Wang et al., 2020). FEZF1-AS1: This lncRNA is implicated in CRC progression through multiple pathways. It regulates the miR-363-3p/PRRX1 axis, promoting cell proliferation, migration, invasion, and EMT. Additionally, FEZF1-AS1 interacts with miR-30a-5p to modulate the expression of NT5E, further contributing to CRC development (Li et al., 2020; Zhang et al., 2021). 3.2 Mechanisms of lncRNA-mediated regulation 3.2.1 Epigenetic regulation LncRNAs can influence CRC progression through epigenetic modifications. For instance, HIF1A-AS2 regulates DNMT3A, a DNA methyltransferase, which can alter the methylation status of various genes involved in cancer progression (Lin et al., 2018). Additionally, global hypomethylation of gene-regulatory regions has been observed during CRC progression, with lncRNAs like H19 being upregulated due to promoter demethylation , which is associated with poor survival in CRC patients (Rokavec et al., 2017). The paper by Matjaz Rokavec, David Horst, and Heiko Hermeking, published in Cancer Research, presents a comprehensive cellular model of colon cancer progression, and highlights the interplay between transcriptional and epigenetic changes during metastasis (Rokavec et. al., 2017). The findings offer insights into the molecular mechanisms underlying colon cancer metastasis and identify potential biomarkers and therapeutic targets for clinical application. 3.2.2 Transcriptional control LncRNAs can also modulate gene expression at the transcriptional level. For example, FEZF1-AS1 regulates the
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