Integrated analysis of mRNA–m⁶A–protein profiles reveals novel insights into the mechanisms for cadmium-induced urothelial transformation

Abstract

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 m⁶A 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 m⁶A 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 m⁶A and proteomics data, but not the transcriptome data. This suggested that m⁶A 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 m⁶A signalling pathways crucial for Cd²⁺ carcinogenesis.

Keywords:

• Cadmium
• carcinogenesis
• RNA sequencing
• proteomic
• m6A

Acknowledgements

The authors thank Editage (www.editage.cn) for English language editing.

Consent for publication

All authors have agreed to publish this manuscript.

Patient consent for publication

Not applicable

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81772699, No. 82073047, No. 81472999], the Key Natural Science Foundation of Guangdong [No. 8151012003000011], the Guangzhou People's Livelihood Science and Technology Project [201803010052], Key Projects of Guangzhou Scientific Research [201804020023], the Project of Guangdong Foundation Construction for Science and Technology [2019B030316024] and the National Key Research and Development Program of China [2016YFC1300600].