Aspartame promotes ovarian cancer progression: A multi-omics study integrating mendelian randomization, network...

The causal relationship between the artificial sweetener aspartame and ovarian cancer (OC), a highly lethal malignancy, remains unclear. This study, therefore, employed a multi-omics approach to investigate this causal link and its potential mechanisms. First, a Mendelian Randomization (MR) analysis indicated that genetically predicted aspartame intake is associated with an increased risk of OC (OR = 2.10, 95 % CI: 1.06-4.18). Next, by integrating network toxicology with machine learning algorithms (LASSO, SVM, and Random Forest), we identified AURKA, CCND1, and RAD51 as potential core target genes. Further validation using multi-omics data from bulk and single-cell RNA sequencing confirmed that these three genes are upregulated in OC tissues. A subsequent MR analysis also provided causal evidence that high expression of CCND1 increases the risk of OC. Furthermore, molecular docking simulations showed that aspartame could form stable bonds with all three target proteins. Finally, in vitro experiments demonstrated that aspartame significantly promoted the malignant phenotypes of OC cells and regulated the expression of these core genes. In conclusion, this study suggests that aspartame may promote ovarian cancer development, potentially by upregulating the expression of key genes such as AURKA, CCND1, and RAD51. These findings provide new evidence for evaluating the safety of aspartame.