Breakthrough could lead to new targets for cancer therapies
Scientists have identified a key genetic switch linked to the development, progression and outcome of cancer, a finding that may lead to new targets for cancer therapies.
The switch, a string of nucleotides dubbed a long non-coding RNA (lncRNA), does not code for proteins like regular RNA. Instead, the scientists found, this particular lncRNA acts as an on/off switch for a key gene whose excessive activity is tied to inflammation and cancer, COX-2.
The COX-2 gene mediates inflammation, which in most cases helps our bodies eliminate pathogens and damaged cells. But inflammation also has a dark side: it aids growth and spread of tumors in the early stages of cancer. By learning more about how COX-2 is affected, scientists may be able to provide a potential target for future cancer treatment.
Senior author Beverly Emerson, a professor in Salk's Regulatory Biology Laboratory and holder of the Edwin K. Hunter Chair, said deciphering the mechanism of COX-2 gene regulation is of great clinical interest.
She said COX-2 is instrumental in the development of several types of cancer, including colon, breast and prostate cancer. Strategies that specifically modulate COX-2 activity could be an attractive treatment approach.
Using human mammary epithelial cells, Emerson and Michal Krawczyk, a senior scientist in Salk's Regulatory Biology Laboratory, discovered that an lncRNA called PACER (p50-associated COX-2 extragenic RNA) teams up with molecules that change the activity of the COX-2 gene.
The scientists demonstrated that PACER kicks a molecule called p50 off of the COX-2 gene, causing COX-2 to go into overdrive. This is the first time scientists have shown that non-coding RNAs must be activated in order to squelch the activity of p50, a gene repressor. In turn, says Krawczyk, blocking p50 promotes the assembly of molecular activators of gene expression, which ramp up COX-2 activity.
The findings have been published online in the journal eLife.
(Posted on 02-05-2014)