Integrated analysis of mRNA–m6A–protein profiles reveals novel insights into the mechanisms for cadmium-induced urothelial transformation
Integrated analysis of mRNA–m6A–protein profiles reveals novel insights into the mechanisms for cadmium-induced urothelial transformation
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DOI：
10.1080/1354750x.2021.1913513
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发表时间：
2021-04
期刊：
影响因子：
2.6
通讯作者：
Bin Wu;Xu Jiang;Yapeng Huang;Xiaoling Ying;Haiqing Zhang;Bixia Liu;Zhuo Li;De-feng Qi;
中科院分区：
文献类型：
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作者：
Bin Wu;Xu Jiang;Yapeng Huang;Xiaoling Ying;Haiqing Zhang;Bixia Liu;Zhuo Li;De-feng Qi;
摘要目的：本研究旨在探讨镉诱导的尿路上皮转化的机制，使用多组学分析（转录组，表转录组和蛋白质组）。研究方法：采用转录组学方法检测基因表达，甲基化RNA免疫沉淀测序方法检测m6A修饰，蛋白质组学方法检测差异表达蛋白。对差异表达基因（DEG）进行基因本体论和京都基因和基因组百科全书富集分析。结果如下：共9491 DEG，711差异表达的蛋白质，和633差异m6A修饰基因之间的镉转化细胞和对照细胞进行了鉴定。大多数基因的调控在不同的组学层次上是不同的。三个组学数据共有57个基因，这些基因在响应DNA损伤刺激和细胞增殖时富集。有趣的是，m6A和蛋白质组学数据共享了13个基因，其中大部分与癌症的发作或进展有关，但转录组数据却没有共享。这表明，m6A修饰是至关重要的转录后调控相关的镉2+诱导的恶性转化。结论：我们的多组学分析提供了一个全面的基因活性的参考图谱，并揭示了m6A信号通路的镉+致癌作用至关重要。
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.