Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 358-367 http://medscipublisher.com/index.php/cge 361 transcription of PRRX1 by sponging miR-363-3p, thereby promoting CRC cell proliferation and invasion (Zhang et al., 2021). Similarly, TTN-AS1 influences the transcription of KLF15 by interacting with miR-376a-3p (Wang et al., 2020). 3.2.3 Post-Transcriptional Regulation Post-transcriptional regulation by lncRNAs involves interactions with microRNAs (miRNAs) and other RNA molecules. HIF1A-AS2 acts as a ceRNA for miR-129-5p, thereby modulating the expression of DNMT3A and promoting CRC progression (Lin et al., 2018). FEZF1-AS1 also functions post-transcriptionally by binding to miR-30a-5p, which affects the expression of NT5E (Li et al., 2020). 3.3 Functional studies and experimental evidence 3.3.1 In vitro studies In vitro studies have provided significant insights into the functional roles of lncRNAs in CRC. For instance, knockdown of HIF1A-AS2 in CRC cell lines resulted in reduced cell proliferation, invasion, and EMT, highlighting its oncogenic role (Lin et al., 2018). Similarly, silencing TTN-AS1 led to decreased cell proliferation and invasion, and increased apoptosis in CRC cells (Wang et al., 2020). FEZF1-AS1 knockdown also inhibited CRC cell migration, invasion, and proliferation in vitro (Li et al., 2020; Zhang et al., 2021). 3.3.2 In vivo studies In vivo studies further corroborate the oncogenic roles of these lncRNAs. Tumor xenograft models have shown that knockdown of TTN-AS1 significantly reduces tumor growth in mice, confirming its role in CRC progression (Wang et al., 2020). FEZF1-AS1 silencing also led to reduced tumor growth in vivo, demonstrating its potential as a therapeutic target (Li et al., 2020; Zhang et al., 2021). 3.4 Clinical relevance and potential as biomarkers The clinical relevance of lncRNAs in CRC is underscored by their potential as biomarkers for diagnosis and prognosis. Elevated levels of HIF1A-AS2, TTN-AS1, and FEZF1-AS1 in CRC tissues are associated with poor prognosis, suggesting their utility as prognostic biomarkers (Lin et al., 2018; Li et al., 2020; Wang et al., 2020; Zhang et al., 2021). Moreover, their involvement in key regulatory pathways makes them attractive targets for therapeutic intervention, offering new avenues for CRC treatment. In summary, lncRNAs such as HIF1A-AS2, TTN-AS1, and FEZF1-AS1 play pivotal roles in CRC progression through various mechanisms, including epigenetic regulation, transcriptional control, and post-transcriptional regulation. Functional studies both in vitro and in vivo highlight their oncogenic potential, and their clinical relevance underscores their promise as biomarkers and therapeutic targets in CRC. 4 miRNAs in Colon Cancer Progression 4.1 Key miRNAs implicated in colon cancer Several miRNAs have been identified as key players in the progression of colon cancer. Notably, miR-181a-5p, miR-145, miR-376a-3p, and miR-34a have been extensively studied for their roles in regulating various aspects of colon cancer biology. miR-181a-5p: This miRNA is involved in the regulation of radiosensitivity in colon cancer cells. It has been shown that miR-181a-5p is upregulated by irradiation and can counteract the effects of lncRNA ANRIL, promoting apoptosis in colon cancer cells (Sun et al., 2021). miR-145: miR-145 is known to regulate colon cancer stem cell proliferation and differentiation. It is negatively regulated by the lncRNA CCAT2, which blocks its maturation process, thereby promoting tumor growth (Yu et al., 2017). miR-376a-3p: This miRNA is targeted by the lncRNA TTN-AS1, which promotes colorectal cancer progression by sponging miR-376a-3p and upregulating KLF15 (Wang et al., 2020).
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==