Integrated Analysis Of Mrna-M(6)A-Protein Profiles Reveals Novel Insights Into The Mechanisms For Cadmium-Induced Urothelial Transformation

Objective: This study aimed to investigate the mechanisms underlying Cd-induced urothelial transformation, using multi-omics analyses (transcriptome, epitranscriptome, and proteome). Methods: Transcriptomics analysis was performed to estimate the expression of genes, methylated RNA immunoprecipitation sequencing analysis was used to detect m(6)A modification, while proteomics analysis was used to identify differentially expressed proteins. Differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Results: A total of 9491 DEGs, 711 differentially expressed proteins, and 633 differentially m(6)A modified genes between Cd-transformed cells and control cells were identified. The regulation of most genes varied at different omics layers. The three omics data shared 57 genes, and these genes were enriched in response to DNA damage stimulus and cell proliferation. Interestingly, 13 genes, most of which are related to the onset or progression of cancer, were shared by the m(6)A and proteomics data, but not the transcriptome data. This suggested that m(6)A modification is crucial for post-transcriptional regulation related to Cd2+-induced malignant transformation. Conclusion: Our multi-omics analysis provided a comprehensive reference map of gene activity and revealed m(6)A signalling pathways crucial for Cd2+ carcinogenesis.