Dicer enzyme brain cancer research took a significant step forward when UNC Lineberger Comprehensive Cancer Center researchers discovered that this DNA repair enzyme plays a critical role in how rapidly dividing tumor cells survive. Now, UNC Lineberger Comprehensive Cancer Center researchers have built on this discovery to uncover a new potential strategy targeting the Dicer enzyme in brain cancer — specifically in medulloblastoma, a common pediatric brain tumor. Published in Cell Reports, the study found that removing Dicer from preclinical medulloblastoma models caused high levels of DNA damage in cancer cells, leading to cell death and increased sensitivity to chemotherapy.
What Is the Dicer Enzyme and Its Role in DNA Repair?
Scientists have known for over a decade that Dicer plays a key role in processing microRNAs, which regulate gene expression in cells. However, it wasn’t until 2012 that researchers discovered Dicer’s direct function in repairing DNA damage, a finding with major implications for brain cancer research. Rapidly dividing cells, including cancer cells, constantly incur DNA damage during division. Chemotherapy and radiation exploit this by further damaging DNA to trigger cell death. Blocking a key DNA repair enzyme like Dicer could make that process significantly more effective.
How the Dicer Enzyme Affects Brain Cancer Tumor Cells
“We found that cancerous cells upregulate Dicer,” said Vijay Swahari, MBBS, MS, postdoctoral fellow at the UNC Neuroscience Center and first author of the study. “We think tumors upregulate Dicer because its function is to repair DNA.” Deshmukh and his team studied the effect of deleting Dicer across several rapidly dividing cell types. In animal models, deleting Dicer from developing brain cells in the cerebellum caused spontaneous DNA damage and severe degeneration. A similar effect was observed in embryonic stem cells.
Medulloblastoma Models Show Promise for Dicer Inhibition
When Dicer was deleted in medulloblastoma models, tumor cells showed high DNA damage levels, reduced tumor load, and greater sensitivity to chemotherapy. “We also took the next step by injecting chemotherapy into models where Dicer was deleted, finding that not only are the tumors smaller, but the tumors are also more sensitive to chemotherapy,” Swahari noted. These findings suggest that Dicer enzyme brain cancer inhibition could be a viable therapeutic strategy.
Implications for Future Brain Cancer Treatment
“We are excited about these results because of the implication that Dicer inhibitors could be developed as a potential therapy for treating rapidly dividing tumors like medulloblastoma,” said Mohanish Deshmukh, PhD, UNC Lineberger member and professor at the UNC School of Medicine. The research opens the door to investigating Dicer as a drug target not only for medulloblastoma but for other brain cancers as well.
This study was supported by grants from the National Institutes of Health.
Why Dicer Enzyme Brain Cancer Research Matters for Clinical Trials
Understanding how tumor cells exploit DNA repair mechanisms like Dicer opens new possibilities for clinical research. Studies targeting enzymes involved in cancer cell survival are particularly valuable because they may reduce the doses of chemotherapy needed, minimizing side effects for patients. For organizations like FOMAT Medical, which supports oncology clinical trials across community-based sites, findings like these represent the kind of translational research that moves from the lab into real-world treatment protocols. Learn more about FOMAT’s oncology clinical trials.
About This Research
Published in Cell Reports | Source: UNC Health | Date: January 2016