Researchers at LMU have found a signaling pathway via which aspirin can can inhibit colorectal most cancers.
Colorectal most cancers, also called bowel most cancers, ranks because the world’s third most prevalent most cancers kind, with roughly 1.9 million new circumstances and 900,000 fatalities yearly. Consequently, there’s a essential demand for preventive measures. Aspirin/acetylsalicylic acid has confirmed to be some of the promising candidates for the prevention of colorectal most cancers.
Among different findings, research have proven that when sufferers with cardiovascular ailments took low doses of aspirin over a number of years, it diminished their danger of colorectal most cancers. Furthermore, aspirin can inhibit the development of colorectal most cancers. Now a staff led by Heiko Hermeking, Professor of Experimental and Molecular Pathology at LMU, has investigated which molecular mechanisms mediate these results.
Molecular Mechanisms Explored
As the researchers report within the journal Cell Death and Disease, aspirin induces the manufacturing of two tumor-suppressive microRNA molecules (miRNAs) referred to as miR-34a and miR-34b/c. To do that, aspirin binds to and prompts the enzyme AMPK, which in flip alters the transcription issue NRF2 such that it migrates into the cell nucleus and prompts the expression of the miR-34 genes. For this activation to succeed, aspirin moreover suppresses the oncogene product c-MYC, which in any other case inhibits NRF2.
Overall, the outcomes present that the miR-34 genes are crucial for mediating the inhibiting impact of aspirin on colorectal most cancers cells. Aspirin was thus unable to forestall migration, invasion, and metastasis in miR-34-deficient most cancers cells. It was already recognized that the miR-34 genes are induced by the transcription issue p53 and mediate its results. “Our results show, however, that activation of the miR-34 genes by aspirin takes place independently of the p53 signaling pathway,” says Hermeking. “This is important because the p53-encoding gene is the most commonly inactivated tumor suppressor gene in colorectal cancer. In most other kinds of cancer, moreover, p53 is inactivated by mutations or viruses in the majority of cases. Aspirin could therefore be employed therapeutically in such cases in the future.”
Reference: “Salicylate induces AMPK and inhibits c-MYC to activate a NRF2/ARE/miR-34a/b/c cascade resulting in suppression of colorectal cancer metastasis” by Chunfeng Liu, Matjaz Rokavec, Zekai Huang and Heiko Hermeking, 28 October 2023, Cell Death & Disease.