Researchers at the University of Le Mans in Germany have discovered the signaling pathway by which aspirin inhibits colorectal cancer, revealing how aspirin inhibits colorectal cancer by activating tumor-suppressing microRNAs. This provides the possibility for aspirin to be used as a preventive and therapeutic drug, especially in cancers with impaired p53 pathway.
Colorectal cancer, also known as intestinal cancer, is the third most common cancer type in the world, with approximately 1.9 million new cases and 900,000 deaths every year. Therefore, the need for preventive measures is urgent. Aspirin/acetylsalicylic acid has proven to be one of the most promising drug candidates for preventing colorectal cancer.
Study results suggest that patients with cardiovascular disease who take low-dose aspirin over several years may reduce their risk of colorectal cancer. In addition, aspirin can inhibit the development of colorectal cancer. Now, a research team led by Heiko Hermeking, professor of experimental and molecular pathology at the University of Munich in Germany, has investigated the molecular mechanisms that mediate these effects.
Researchers reported in the journal Cell Death and Disease that aspirin can induce the production of two tumor-suppressing microRNA molecules (miRNA), namely miR-34a and miR-34b/c. To this end, aspirin binds to and activates the AMPK enzyme, which in turn changes the transcription factor NRF2, causing it to migrate into the nucleus and activate the expression of the miR-34 gene. For this activation to be successful, aspirin also inhibits the oncogene product c-MYC, which would otherwise inhibit NRF2.
In conclusion, the research results indicate that the miR-34 gene is necessary to mediate the inhibitory effect of aspirin on colorectal cancer cells. Therefore, aspirin cannot prevent the migration, invasion and metastasis of miR-34-deficient cancer cells. It is already known that the miR-34 gene is induced by the transcription factor p53 and mediates its effects.
"However, our results indicate that activation of the miR-34 gene by aspirin is independent of the p53 signaling pathway," Hermeking said. "This is important because the gene encoding p53 is the most commonly inactivated tumor suppressor gene in colorectal cancer. Furthermore, in most other types of cancer, p53 is inactivated in most cases by mutations or viruses. Therefore, aspirin could be used in the future to treat such cases."
Compiled source: ScitechDaily