UNC researchers find new genetic target for a different kind of cancer drug

PUBLIC RELEASE DATE:

8-Sep-2014

Contact: Mark Derewicz mark.derewicz@unchealth.unc.edu 919-923-0959 University of North Carolina Health Care http://www.twitter.com/UNC_Health_Care

CHAPEL HILL, NC Researchers from the UNC School of Medicine have discovered that the protein RBM4, a molecule crucial to the process of gene splicing, is drastically decreased in multiple forms of human cancer, including lung and breast cancers. The finding, published today in the journal Cancer Cell, offers a new route toward therapies that can thwart the altered genetic pathways that allow cancer cells to proliferate and spread.

"Historically, scientists haven't targeted the proteins in cancer cells that are involved in gene splicing," said Zefeng Wang, PhD, associate professor in the department of pharmacology and senior author of the Cancer Cell paper. "This is a whole new ballgame in terms of gene regulation in cancer."

There are approximately 25,000 genes in the human genome the same amount as in a fruit fly. But in humans, these genes are spliced together in different ways to create various kinds of messenger RNA to produce the many different proteins humans require. It's like a filmmaker splicing together bits of movie scenes to create alternative cuts of a movie. In genetics, this process is called alternative splicing.

Wang's lab found that RBM4 is an important film editor.

Wang, a member of the UNC Lineberger Comprehensive Cancer Center, studies how alternative splicing happens in normal cells and in cancer cells. Through a series of biochemical experiments and high-throughput screening methods, his team identified about 20 proteins that are involved in regulating alternative splicing. Then his team conducted further experiments to pinpoint changes in the activity of these proteins in various kinds of human cancer cells and in mouse models. Such "misregulated" protein expression would provide evidence that the proteins are involved in cancer development or metastasis.

Wang found that the protein RBM4 was decreased, as compared with normal tissue. In lung and breast cancer patients, RBM4 was drastically "down regulated."

"In normal cells, RBM4 inhibits alternative splicing," Wang says. "It makes genes splice from a long form into a short form. For one of the genes we study, which is called Bcl-x, we want the short form because it has anti-cancer properties."

See the article here:
UNC researchers find new genetic target for a different kind of cancer drug