Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 358-367 http://medscipublisher.com/index.php/cge 363 5.3 Impact on gene expression and pathways in colon cancer The interactions between lncRNAs and miRNAs have profound effects on gene expression and signaling pathways in colon cancer. For instance, the lncRNA MALAT1 has been implicated in the regulation of various biological processes, including cell proliferation, apoptosis, and migration, by acting as a ceRNA for multiple miRNAs (Su et al., 2021). In colon adenocarcinoma, a specific ceRNA network involving lncRNAs, miRNAs, and mRNAs has been identified, which includes key players such as HOTAIR, miR-143, and SERPINE1, all of which are significantly correlated with overall survival (Wang et al., 2019b). Furthermore, the lncRNA MAGI2-AS3 has been shown to promote gastric cancer progression by sponging miR-141/200a, thereby maintaining the overexpression of ZEB1, a key regulator of epithelial-mesenchymal transition (EMT) (Li et al., 2019). These findings illustrate the critical role of lncRNA-miRNA interactions in modulating gene expression and pathways that drive colon cancer progression. 6 Therapeutic Implications 6.1 Targeting lncRNAs for colon cancer therapy 6.1.1 RNA interference approaches RNA interference (RNAi) is a promising strategy for targeting long non-coding RNAs (lncRNAs) in colon cancer therapy. Silencing specific lncRNAs that are implicated in cancer progression can inhibit tumor growth and metastasis. For instance, the lncRNA HNF1A-AS1 has been shown to promote colon cancer cell viability, migration, and invasion. Silencing HNF1A-AS1 using RNAi techniques impaired tumor growth and metastasis in xenograft models, suggesting its potential as a therapeutic target (Fang et al., 2017). Similarly, targeting lncRNA MALAT1, which regulates the miR-129-5p/HMGB1 axis, can inhibit colon cancer cell proliferation and progression (Wu et al., 2018). 6.1.2 Small molecule inhibitors Small molecule inhibitors that specifically target lncRNAs or their interactions with other molecules represent another therapeutic approach. These inhibitors can disrupt the function of oncogenic lncRNAs, thereby impeding cancer progression. For example, the lncRNA MALAT1 has been implicated in various cancers, including colon cancer, by acting as a competing endogenous RNA (ceRNA) to regulate gene expression (Su et al., 2021). Developing small molecules that can inhibit MALAT1's interaction with miR-129-5p could provide a novel therapeutic strategy for colon cancer (Wu et al., 2018). 6.2 Targeting miRNAs for colon cancer therapy 6.2.1 miRNA mimics and inhibitors MiRNA-based therapies involve the use of miRNA mimics or inhibitors to restore normal gene expression. MiRNA mimics can replenish tumor-suppressive miRNAs that are downregulated in cancer, while miRNA inhibitors can block the function of oncogenic miRNAs. For instance, miR-34a, a tumor-suppressive miRNA, is downregulated in colon cancer. Restoring miR-34a levels using miRNA mimics can inhibit cancer cell proliferation and metastasis (Fang et al., 2017). Conversely, inhibiting oncogenic miRNAs such as miR-141/200a, which are involved in the regulation of lncRNA MAGI2-AS3, can suppress tumor progression (Li et al., 2019). 6.2.2 Delivery systems and strategies Effective delivery systems are crucial for the success of miRNA-based therapies. Nanoparticles, liposomes, and viral vectors are commonly used to deliver miRNA mimics or inhibitors to target cells. These delivery systems protect miRNAs from degradation and enhance their uptake by cancer cells. For example, nanoparticles have been used to deliver miR-34a mimics to colon cancer cells, resulting in significant tumor suppression (Ding et al., 2018). Additionally, exosome-mediated delivery of miRNAs has shown promise in targeting specific cancer cells and modulating the tumor microenvironment (Liang et al., 2020). 6.3 Combination therapies involving lncRNAs and miRNAs Combining lncRNA and miRNA-based therapies can enhance therapeutic efficacy by simultaneously targeting multiple pathways involved in cancer progression. For instance, targeting both lncRNA HNF1A-AS1 and miR-34a can disrupt the miR-34a/SIRT1/p53 feedback loop, leading to reduced tumor growth and metastasis
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