Talk with Dr. Chang on microRNAs and Cancer

Interview host (denoted as Q below): This year, the Nobel Prize is awarded to two prominent scientists for their contributions to the field of microRNA. It is our pleasure to have Alice Chang, Ph.D., from CMU Institute of Biochemistry, here with us to talk about microRNA and Cancer. Thank you for joining us today, Dr. Chang. To start, could you explain what microRNAs are and why they’re important in the context of cancer?

Dr. Chang: Thank you for having me. MicroRNAs, or miRNAs, are small, non-coding RNA molecules that regulate gene expression after transcription. Despite being encoded by only about 3% of our genes, they can influence the expression of approximately 30% of protein-coding genes. This makes them incredibly significant in various biological functions, including development, metabolism, and particularly cancer. In cancer, miRNAs can act as tumor suppressors or oncomiRs, depending on the cellular context.

Q: Speaking of cancer, how exactly do miRNAs contribute to tumor development and progression?

Dr. Chang: The role of miRNAs in cancer is a major area of study. Dysregulation of miRNAs can lead to oncogenesis by disrupting the balance between oncogenes and tumor suppressor genes. For example, the first significant evidence of miRNA involvement in cancer was discovered in chronic lymphocytic leukemia. Researchers found that miR-15 and miR-16 were deleted or downregulated in many CLL cases, leading to the overexpression of Bcl2, an antiapoptotic protein. This relationship showcases how miRNAs can directly influence tumor survival and growth.

Q: That’s a compelling example. Can you talk about the connection between miRNAs and cancer stem cells?

Dr. Chang: Cancer stem cells (CSCs) are a subpopulation of tumor cells with the ability to drive tumor initiation, progression, and recurrence. miRNAs are key regulators of CSC behavior. Dysregulation of specific miRNAs can lead to an expanded CSC population, which is often associated with more aggressive tumor characteristics. Understanding how miRNAs influence CSCs can help us develop targeted therapies aimed at eradicating these resilient cancer cells.

Q: What therapeutic approaches are being explored involving miRNAs?

Dr. Chang: miRNA-based therapies are an exciting frontier in cancer treatment. There are two main strategies: inhibiting oncomiRs and restoring the function of tumor-suppressive miRNAs. Clinical trials are actively investigating these approaches. For

instance, using antisense oligonucleotides to inhibit specific oncomiRs could reduce tumor growth. Additionally, delivering miRNA mimics to restore the expression of tumor suppressors offers another promising avenue.

Q: Delivery seems crucial. What challenges exist in effectively delivering miRNA therapies?

Dr. Chang: You’re correct; delivery is a significant challenge. miRNAs are relatively unstable and need to be delivered effectively to target tissues without triggering off-target effects. Various delivery systems are being developed, including lipid nanoparticles, viral vectors, and exosomes. These systems aim to enhance stability, improve bioavailability, and ensure specific targeting of cancer cells.

Q: Are there any recent advancements in the field that stand out to you?

Dr. Chang: Yes, there are several exciting developments. Research is increasingly focusing on the role of specific miRNAs in tumor biology, including their potential as biomarkers for prognosis and treatment response. Additionally, novel delivery systems are being optimized to enhance the effectiveness of miRNA therapies. For example, studies have shown that combining miRNA therapies with existing treatments like chemotherapy can synergistically improve outcomes.

Q: How do you envision the future of miRNA research and its impact on cancer treatment?

Dr. Chang: I believe the future of miRNA research holds great promise. As we better understand the intricate roles miRNAs play in cancer biology, we can develop more targeted and personalized therapeutic strategies. The goal is to create miRNA-based treatments that are not only effective but also minimize side effects by specifically targeting cancer cells while sparing normal tissues.

Q: That sounds like a hopeful direction. Is there anything else you’d like to add about the importance of miRNAs in cancer research?

Dr. Chang: I’d like to emphasize that miRNAs represent a crucial layer of regulatory control in cancer. Their multifaceted roles in gene regulation, immune modulation, and stem cell behavior make them promising targets for innovative therapies. Continued research in this area will undoubtedly lead to breakthroughs that can significantly improve cancer management and patient outcomes.

Q: Thank you, Dr. Chang, for sharing your insights on the role of microRNAs in cancer research. It’s been a pleasure!

Dr. Chang: Thank you for having me. It’s an exciting field, and I appreciate the opportunity to discuss it.

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