Channels, Fall 2021

Page 6 Hines, Marcum, Strong, Wade • Differential MicroRNA Expression will prevent the cells from continuing to grow and even cause an increase of apoptosis (Mollaei et al., 2019). After discussing the strategies behind using miRNAs to treat cancer types, it is important to understand how these theoretical therapies could be integrated into clinical medicine. Currently, biomedical researchers are investigating four main methods of drug delivery: anti-miRNA nucleotides, viral delivery, nonviral delivery, and small molecule drugs (Lee et al., 2020). The first type of delivery is the anti-miRNA nucleotides. RNA molecules are made more chemically stable by altering their sugar-phosphate background, which makes them less susceptible to degradation within the cell. By making RNA molecules more stable, certain nucleotide sequences could be synthesized and used to create anti-miRNA oligonucleotides that decrease the levels of specific miRNAs. Studies in mice have shown that this RNA modification can be successfully used to target a certain miRNA and decrease its expression within the cell in vivo (Lee et al., 2020). The second delivery strategy, viral delivery, has been studied for years as a mechanism to edit genes and change gene expression. In the case of cancer treatment, viruses can be used to control gene expression and limit harmful side effects, and viruses may also be able to remove certain destructive genes completely. For instance, a drug called Luxturna uses viral delivery to alter gene expression and treat Huntington’s disease by downregulating the Huntington gene (Lee et al., 2020). While this has not been used in clinical settings with cancer, it shows promising results as a therapeutic treatment. Nonviral delivery, the third method for delivery of treatment, includes polymeric vectors, lipids, and both inorganic and RNA nanoparticles. The goal of nonviral delivery is to allow the body to take up the drug without eliciting any immune response or causing the miRNAs to become completely degraded (Lee et al., 2020). The nonviral delivery methods described above have been proven to be safer for patients when compared to viral delivery, minimizing harmful side effects. The final delivery strategy that could be used to target miRNAs is the use of small molecule drugs. These drugs can be used to target specific miRNAs and transcription factors, changing the level of expression by inhibiting or inducing them (Lee et al., 2020). Small molecule drugs appear to be safe and effective for clinical use and may be able to help regulate the miRNA expression in a way that slows cancer progression in patients. Conclusion Summary of Findings Based on the way microRNAs (miRNAs) are upregulated or downregulated in cancerous tumors, specifically glioblastoma, there are two types of therapy that are being explored as potential treatments—miRNA reduction therapy and miRNA restoration therapy. MiRNA reduction therapy targets upregulated miRNAs and downregulates them in cancer patients to slow the progress of malignancies. MiRNA restoration therapy theoretically upregulates downregulated tumor suppressor miRNAs to also help slow cancer progression. Biomarkers can be used for diagnosing cancerous tumors. This is done by finding the specific miRNAs that are upregulated and downregulated in comparison with normal health brain tissue.

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