University of Florida researchers have identified specific human genes targeted by a virus believed to cause Kaposi's sarcoma, a rare form of cancer associated with AIDS and with organ transplants that causes patches of red or purple tissue to grow under people's skin.
Writing in PLOS Pathogens, the scientists are the first to name human genes that are actually hijacked by a virus wielding minimolecules called microRNAs.
Scientists believe these viral microRNAs silence genes that suppress tumor cells and keep vascular growth in check, resulting in the rampant blood vessel growth typical of Kaposi's sarcoma.
“The hallmarks of Kaposi's sarcoma are red spots full of blood vessels on the necks, arms and legs of patients,” said Rolf Renne, Ph.D., an associate professor of molecular genetics and microbiology at the College of Medicine and a member of the UF Shands Cancer Center and the UF Genetics Institute. “We think that the tumor virus is using microRNAs to make sure infected cells are well-nourished and protected from the human immune system.”
Thought to be little more than cellular debris less than a decade ago, microRNAs are short chemical strands that strategically disable genes by binding to them. They play a role in healthy development — no one with a complete set of fingers and toes would want their genes to keep adding new digits — and they evidently may be involved in the onset of some diseases, including cancer.
Now it seems that even foreign microRNA has a say in human health.
In an effort to identify human gene targets, UF scientists equipped cultured human cells with just 10 genes from the Kaposi's sarcoma virus, thus endowing human cells with the ability to produce viral microRNA. Scientists then screened the more than 30,000 genes that exist within human cells and found that 81 were strongly inhibited in the presence of the viral microRNAs.
Five of the most affected genes are known to suppress tumor and blood vessel growth and influence the body's immune response, suggesting that the virus uses microRNAs to create a cancerous environment in which it thrives, undetected by the body's natural defenses.
Researchers confirmed the results of the microRNA gene profiling with tests to detect individual microRNA activity in specific genes.
“The data beautifully showed which genes were regulated by the viral microRNA,” said Henry Baker, Ph.D., a professor and interim chairman of molecular genetics and microbiology who oversaw the gene screening. “The most exciting thing was one of the most-targeted genes on the list is thrombospondin 1. When something is important in a natural process, there are often a lot of built-in redundancies. In this case all of the viral microRNAs were used to target 34 different binding sites on the human gene, so apparently this is a virus that really wants to down regulate thrombospondin.”