Removal of Enzyme May Improve Brain Cancer Treatment

Researchers have found that the removal of the Dicer enzyme plays a significant role in medulloblastoma, a common type of brain cancer in children.

For over a decade, scientists saw the importance that Dicer played in processing cellular microRNAs (the regulation of gene expression in cells).

In 2012, scientists realized that there was a direct role that Dicer held in the repairing of DNA damage. This function is important to cancer research because cancer cells that rapidly divide create damage as during this process. Chemotherapy and radiation, which is used to create cell death, damages the cellular DNA.

If you remove the enzyme responsible for repairing the DNA in cancerous cells, it could potentially help prevent DNA repair, according to the study.

"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," said Lineberger member Mohanish Deshmukh, PhD. "We have found that targeting Dicer could be an effective therapy to either prevent cancer development or to actually sensitize tumors to chemotherapy."

When researchers deleted Dicer in normal and rapidly dividing developing brain cells in the cerebellum of animal models, they found spontaneous DNA damage in the brain cells, which led to the degeneration of the cerebellum.

Looking to see if Dicer had a similar effect on the cells outside of the brain, investigators found a similar effect. When they deleted Dicer in medulloblastoma models, the cells had high DNA damage and degeneration.

This caused the tumor load to be lower and the cancerous cells were much more sensitive to chemotherapy.

"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," Deshmukh said.