Authors: Emily Brown, Future Science Group
The enzyme Dicer is known to play a key role in the repair of the DNA damage that can occur during DNA replication in rapidly dividing cells. This week, a new study published in Cell Reports has demonstrated that the elimination of Dicer from cancer cells in a preclinical model of medulloblastoma promoted death of the malignant cells – a finding that suggests Dicer could be a novel therapeutic target in the disease.
As author Mohanish Deshmukh of the University of North Carolina Lineberger Comprehensive Cancer Center (NC, USA) explained: “This is the first time that the specific function of Dicer for DNA damage has been looked at in the context of the developing brain or even in brain tumors, despite that the fact that the protein has been extensively studied. We have found that targeting Dicer could be an effective therapy to either prevent cancer development or to actually sensitize tumors to chemotherapy.”
In this study, Deshmukh and his team tested the consequences of deleting Dicer in several rapidly dividing cells types, including developing brain cells and embryonic stem cells, resulting in spontaneous DNA damage. Upon deletion of Dicer within medulloblastoma models, cells were observed to have high levels of DNA damage and degeneration. Tumor cells that were lacking Dicer were also observed to be smaller and more chemosensitive.
“We found that cancerous cells upregulate Dicer,” commented Vijay Swahari, first author of the study of the University of North Carolina Neuroscience Center. “We think tumors upregulate Dicer because its function is to repair DNA.”
Swahari continued: “We found that when you delete Dicer, these tumors are more sensitive to DNA damage. 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.”
As a result of their findings, the team postulate that Dicer could be investigated as a potential drug target for medulloblastoma and other types of brain cancer.
Source: UNC Health Care press release