LMU researchers have identified a signaling pathway by which aspirin can suppress colorectal cancer.
Colorectal cancer (bowel cancer) is the third most common form of cancer in the world, with approximately 1.9 million new diagnoses and 900,000 deaths each year. Therefore, preventive substances represent an urgent clinical need. Aspirin/acetylsalicylic acid has proven to be one of the most promising candidates for the prevention of colorectal cancer.
Among other findings, studies have shown that when patients with cardiovascular disease take low doses of aspirin over several years, their risk of colorectal cancer decreases. Additionally, aspirin can inhibit the progression of colorectal cancer. Now, a team led by Heiko Helmeking, professor of experimental and molecular pathology at LMU, investigated which molecular mechanisms mediate these effects.
as a researcher report in diary cell death and disease, aspirin induces the production of two tumor suppressor microRNA molecules (miRNAs) called miR-34a and miR-34b/c. To do this, aspirin binds to and activates the enzyme AMPK, which in turn alters the transcription factor NRF2 to move to the cell nucleus and activate expression of the miR-34 gene.
To ensure this activation is successful, aspirin further suppresses the oncogene product c-MYC, which inhibits NRF2.
Overall, the results indicate that the miR-34 gene is required to mediate the inhibitory effects of aspirin on colorectal cancer cells. Therefore, aspirin failed to prevent migration, invasion, and metastasis of miR-34-deficient cancer cells. It was already known that the miR-34 gene is induced by the transcription factor p53 and mediates its effects.
“However, our results show that activation of the miR-34 gene by aspirin occurs independently of the p53 signaling pathway,” Hermeking says.
“This is important because the gene encoding p53 is the most commonly inactivated tumor suppressor gene in colorectal cancer. Furthermore, in most other cancer types, p53 is almost always suddenly It is inactivated by mutations or viruses. Therefore, aspirin could be used therapeutically in such cases in the future. ”
For more information:
Chunfeng Liu et al., Salicylic acid induces AMPK, inhibits c-MYC, activates NRF2/ARE/miR-34a/b/c cascade, and suppresses colorectal cancer metastasis. cell death and disease(2023). DOI: 10.1038/s41419-023-06226-9
Quote: Colorectal cancer: Aspirin found to activate protective genes (November 2, 2023) From https://medicalxpress.com/news/2023-11-colorectal-cancer-aspirin-genes.html 2023 Retrieved November 5, 2017
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