Aspirin’s ability to prevent cardiovascular disease and colon cancer is a known attribute of the pain reliever, but researchers do not fully understand how it exerts such diverse benefits. Now, a study has identified a new mechanism of aspirin’s actions that might offer an explanation.
The study, “Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer“, published in EBioMedicine, reveals that aspirin affects the function of a regulatory protein, called RUNX1, which is involved in both the function of platelets and suppression of colon tumors.
“This research identifies a new way in which aspirin works that was not predicted based on the known pharmacology,” Deepak Voora, MD, assistant professor in Duke’s Center for Applied Genomics & Precision Medicine, said in a press release.
Aspirin is among the most commonly used medications to prevent cardiovascular disease and colon cancer. Aspirin’s pain-reducing and blood-thinning effects have been traced to its ability to suppress COX1 function, a protein that is involved in both inflammation and blood clotting.
“But COX-1 has only partially explained how aspirin works for cardiovascular health, and it has not been shown to be implicated in cancer at all,” Voora said.
Voora and colleagues already had identified an aspirin response signature, which consisted of a panel of genes whose expression was modified upon aspirin exposure and correlated with aspirin’s effects on platelets and heart attack. In this study, the researchers sought to identify a transcription factor (a protein that binds to DNA and regulates the expression of specific genes) whose function could be directly regulated by aspirin and, as a consequence, affect “aspiring response signature gene expression.”
The researchers found that the RUNX1 protein was a possible candidate. This master regulator was able to regulate 60 percent of the genes included in the aspirin response signature, and was directly regulated by aspirin. Importantly, RUNX1 expression was linked with improved long-term clinical outcomes in patients with cardiovascular disease and colon cancer, suggesting this is how aspirin exerts its effects in preventing those diseases.
“This approach to comprehensively evaluate the actions of a drug using genomic data—as we have done here with aspirin—is a paradigm shift that could change how drugs are developed and positioned for clinical use,” said co-author Geoffrey Ginsburg, MD, director of the Center for Applied Genomics & Precision Medicine. “We intend to use this approach to explore the pleiotropic effects of drugs more broadly to anticipate their side effects and understand their full repertoire of actions clinically.”
