Researchers have actually exposed how aspirin prevents colorectal cancer by activating tumor-suppressing microRNAs, using potential for its use as a healing and preventive representative, especially in cancers where the p53 pathway is compromised.Researchers at LMU have actually discovered a signaling path through which aspirin can prevent colorectal cancer.Colorectal cancer, likewise understood as bowel cancer, ranks as the worlds third most widespread cancer type, with roughly 1.9 million new cases and 900,000 casualties yearly. Consequently, there is a critical demand for preventive measures. Aspirin/acetylsalicylic acid has proven to be among the most promising prospects for the prevention of colorectal cancer.Among other findings, studies have revealed that when clients with heart diseases took low doses of aspirin over several years, it reduced their risk of colorectal cancer. Aspirin can prevent the development of colorectal cancer. Now a group led by Heiko Hermeking, Professor of Molecular and experimental Pathology at LMU, has actually examined which molecular systems mediate these effects.Molecular Mechanisms ExploredAs the scientists report in the journal Cell Death and Disease, aspirin induces the production of 2 tumor-suppressive microRNA molecules (miRNAs) called miR-34a and miR-34b/ c. To do this, aspirin binds to and triggers the enzyme AMPK, which in turn changes the transcription factor NRF2 such that it migrates into the cell nucleus and triggers the expression of the miR-34 genes. For this activation to be successful, aspirin additionally suppresses the oncogene item c-MYC, which otherwise hinders NRF2.Overall, the results show that the miR-34 genes are necessary for moderating the preventing result of aspirin on colorectal cancer cells. Aspirin was therefore not able to prevent migration, invasion, and transition in miR-34-deficient cancer cells. It was currently known that the miR-34 genes are induced by the transcription factor p53 and mediate its effects. “Our results reveal, however, that activation of the miR-34 genes by aspirin takes location individually of the p53 signaling path,” says Hermeking. “This is necessary since the p53-encoding gene is the most typically inactivated tumor suppressor gene in colorectal cancer. In most other sort of cancer, moreover, p53 is suspended by mutations or viruses in the bulk of cases. Aspirin might therefore be utilized therapeutically in such cases in the future.” Reference: “Salicylate causes AMPK and inhibits c-MYC to activate a NRF2/ARE/miR -34 a/b/c waterfall resulting in suppression of colorectal cancer transition” by Chunfeng Liu, Matjaz Rokavec, Zekai Huang and Heiko Hermeking, 28 October 2023, Cell Death & & Disease.DOI: 10.1038/ s41419-023-06226-9.