Research studies have been increasingly focusing on the role of long non-coding RNAs and their association with various diseases including cancer. 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 inflammation and Cancer.
The Cox-2 gene is responsible for the inflammation response which acts against pathogens and damaged cells. However, the inflammation response can contribute to the growth and spread of tumors at the early stages of cancer.
“Deciphering the mechanism of COX-2 gene regulation 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 cancer, including colon, breast and prostate cancer. 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, cancer cells often shut off COX-2 activity, as if at that stage COX-2 is no longer beneficial for tumor growth because it exposes spreading tumor cells 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