Researchers report that at least one tumor suppressor gene is in fact turned off by a noncoding RNA that is antisense to the sense gene. “This is the first time we’ve seen an antisense RNA silencing a tumor suppressor through the means of epigenetic changes,” according to Hengmi Cui, Ph.D., assistant professor of molecular medicine at Johns Hopkins University (JHU) and one of the authors of the paper.
The scientists first surveyed computer databases for tumor suppressor genes with known neighboring antisense RNAs. They found antisense counterparts to 21 well-known tumor suppressor genes and decided to further study one of them, p15. This gene is reportedly deleted or silenced in several types of human cancer including melanomas, gliomas, lung and bladder carcinomas, and up to 60% of leukemias.
The JHU team first analyzed leukemia cells for the presence of antisense p15. Of 16 patient samples, 11 showed an increase in antisense p15 and decreased p15. Further experiments showed that chemically turning on the antisense gene turned off the sense p15 gene.
“Somehow, the presence of the antisense RNA leads to the formation of this tightening of the chromosome to make heterochromatin around the p15 gene, turning it off,” explains author Andrew Feinberg, M.D., professor of medicine, oncology, molecular biology, and genetics and director of the Epigenetics Center at JHU. “We’re now looking at other tumor suppressor genes to figure out how this happens and how general this phenomenon is.”
Researchers from NCI were also involved in the study. The paper is published in the January 10 issue of Nature.