Prehistoric Virus May Be Key to Fighting Certain Types of Cancer

August 29, 2017 | by Katie Neith

Morris-Kevin Kevin V. Morris, Ph.D., professor and associate director of the Center for Gene Therapy at the Beckman Research Institute
Ribonucleic acid, or RNA, is a type of molecule found in all living cells and is essential for cellular function. City of Hope’s Kevin V. Morris, Ph.D., professor and associate director of the Center for Gene Therapy at the Beckman Research Institute, is a leader in RNA research and was the first to recognize the unique properties of non-coding RNA. Now, he and a team of researchers have figured out the mechanism behind a non-coding RNA’s control of a gene involved in some cancers.  
 
Their findings were outlined in a study, “The molecular dynamics of long non-coding RNA control of transcription of PTEN and its pseudogene,” published online in the August 28 issue of the Proceedings of the National Academy of Sciences (PNAS) journal.
 
“Genes, including those involved in cell cycle and cancer progression, are regulated by a complex, underappreciated RNA-based mechanism,” said Morris, whose study collaborators include City of Hope graduate student Galina Shevchenko and researchers from Australia and Sweden. “The data in this paper shows that a tumor suppressor gene — called PTEN — is under the regulation of long non-coding RNAs.”
 
But it’s not just any kind of long non-coding RNA; it’s a pseudogene  long non-coding RNA. Pseudogenes are prehistoric viruses that have been with humans since they evolved from primates and were traditionally considered non-functional junk floating around the human body. But previous work by Morris and others showed that these pseudogenes can, indeed, be active.
 
“In this study we found that, basically, a prehistoric virus gene that’s a non-coding transcript is controlling the PTEN tumor suppressor gene,” said Morris.
 
This is important because in glioblastomas and skin cancer, the PTEN tumor suppressor gene is not active. And without PTEN, patients die relatively quickly due to a loss of control over the cell cycle, according to Morris.
 
“What this means for cancer is that we can now target these particular RNAs with small molecules and/or nucleic-acid-based drugs to activate specific tumor suppressor genes and hopefully better treat the cancers that progress because of a loss of PTEN functionality,” he said.
 
Morris and his team are now actively working with Jacob M. Berlin, Ph.D., associate professor in the Department of Molecular Medicine at City of Hope, and his lab to develop approaches to specifically target these non-coding RNAs, including the use of nanotechnology.
 
“Our findings offer a very specific approach to target and regulate or activate the PTEN gene in people with cancer,” said Morris.
 
The project highlighted in the PNAS journal article was supported by the National Institute of Allergies and Infectious Disease (P01 AI099783-01), the National Institutes of Health (DK104681-02), an Australian Research Council Future Fellow grant and various Swedish cancer organizations.
 

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