Cancer switched on and off by long non-coding RNAs.

rnaResearch studies have been increasingly focusing on the role of long non-coding RNAs and their association with various diseases including . A new study by the Salk Institute for Biological Studies identified that long non-coding RNAs act as an on/off switch for the COX-2 gene which is tied to and .

The Cox-2 gene is responsible for the response which acts against and damaged cells. However, the response can contribute to the growth and spread of tumors at the early stages of .

“Deciphering the mechanism of COX-2 is of great clinical interest,” says senior author Beverly Emerson, a professor in Salk’s Regulatory Biology Laboratory and holder of the Edwin K. Hunter Chair. “COX-2 is instrumental in the development of several types of , including colon, breast and prostate . Strategies that specifically modulate COX-2 activity could be an attractive treatment approach.”

Human mammary epithelial cells were used and it was discovered that a long non coding RNA strand called PACER (p50-associated COX-2 extragenic RNA) combines with molecules that change the activity of the COX-2 gene. PACER acts by removing a molecule called p50 from 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 stop the activity of p50, a gene repressor. Blocking p50 promotes the assembly of molecular activators of gene expression, which gears up COX-2 activity.

Early in the disease process, instead of activating the immune system to clear malignant cells from the body, COX-2 aids the growth and spread of tumors. In later stages of disease, cells often shut off COX-2 activity, as if at that stage COX-2 is no longer beneficial for because it exposes spreading to the immune system. That presents the opportunity to trigger COX-2 expression via PACER in late-stage cancers to aid immune system clearance of metastatic cells.

“This could be a potential treatment for late-stage cancers,” said Krawczyk. “We could possibly use small molecules to reactivate COX-2 activity, or perhaps even supply PACER itself, to fight the disease.”


M. Krawczyk, B. M. Emerson. p50-Associated COX2 Extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF- B complexes. eLife, 2014; DOI: 10.7554/eLife.01776

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