Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 358-367 http://medscipublisher.com/index.php/cge 362 miR-34a: miR-34a is part of a feedback loop involving the lncRNA HNF1A-AS1 and SIRT1/p53. HNF1A-AS1 represses miR-34a, leading to enhanced metastatic progression of colon cancer (Fang et al., 2017). 4.2 Mechanisms of miRNA-mediated regulation miRNAs can induce mRNA degradation by binding to complementary sequences in the 3'-untranslated regions (3'-UTRs) of target mRNAs. For instance, miR-145 targets mRNAs involved in colon cancer stem cell proliferation, leading to their degradation and reduced expression (Yu et al., 2017). In addition to mRNA degradation, miRNAs can inhibit the translation of target mRNAs. miR-181a-5p, for example, binds to the lncRNA ANRIL, preventing it from exerting its effects on radiosensitivity and promoting apoptosis through translational inhibition (Sun et al., 2021). In vitro studies have provided significant insights into the roles of miRNAs in colon cancer. For example, the overexpression of miR-181a-5p in colon cancer cell lines has been shown to increase apoptosis and reduce cell viability following irradiation (Sun et al., 2021). Similarly, the knockdown of CCAT2, which increases miR-145 levels, impairs colon cancer stem cell proliferation and differentiation (Yu et al., 2017).In vivo studies further validate the roles of miRNAs in colon cancer progression. Tumor xenograft models have demonstrated that the knockdown of TTN-AS1, which increases miR-376a-3p levels, inhibits tumor growth and invasion (Wang et al., 2020). Additionally, silencing HNF1A-AS1 in xenograft models reduces tumor growth and metastasis by upregulating miR-34a (Fang et al., 2017). 4.3 Clinical relevance and potential as biomarkers miRNAs hold significant potential as biomarkers for colon cancer diagnosis and prognosis. Elevated levels of miR-181a-5p, miR-145, miR-376a-3p, and miR-34a have been associated with various clinical outcomes in colon cancer patients. For instance, high miR-181a-5p levels correlate with increased radiosensitivity and better patient outcomes (Sun et al., 2021). Similarly, miR-145 and miR-34a levels are linked to reduced tumor growth and metastasis, making them promising targets for therapeutic interventions (Fang et al., 2017; Yu et al., 2017). The clinical relevance of these miRNAs underscores their potential as biomarkers for early detection and personalized treatment strategies in colon cancer. 5 Interactions Between lncRNAs and miRNAs 5.1 Competing endogenous RNA (ceRNA) networks Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) by sequestering microRNAs (miRNAs) and preventing them from binding to their target mRNAs. This interaction modulates the expression of genes involved in various cellular processes, including those critical for cancer progression. For instance, the lncRNA UBE2CP3 has been shown to promote gastric cancer progression by acting as a ceRNA for miR-138-5p, thereby upregulating ITGA2 (Li et al., 2021). Similarly, in colorectal cancer (CRC), lncRNA TTN-AS1 sponges miR-376a-3p to upregulate KLF15, promoting cancer cell proliferation and invasion (Wang et al., 2020). Another example is the lncRNA PART1, which sponges miR-150-5p and miR-520h to upregulate CTNNB1, thereby activating the Wnt/β-catenin pathway in CRC (Zhou et al., 2019). These ceRNA networks highlight the intricate regulatory roles of lncRNAs in cancer biology. 5.2 Mutual regulation mechanisms The mutual regulation between lncRNAs and miRNAs is a complex and dynamic process that significantly impacts gene expression and cancer progression. For example, the lncRNA CCAT2 has been found to regulate miR-145 by inhibiting its maturation process in colon cancer cells, thereby affecting cancer stem cell proliferation and differentiation (Yu et al., 2017). Additionally, lncRNA HIF1A-AS2 has been shown to regulate colorectal cancer progression by binding to miR-129-5p, which in turn affects the expression of DNMT3A, a gene involved in DNA methylation and gene silencing (Lin et al., 2018). These interactions underscore the bidirectional regulatory mechanisms between lncRNAs and miRNAs, which can either promote or inhibit cancer progression depending on the context.
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