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Aberrant DNA Methylation in Dimethylarsinic Acid-induced Rat Bladder Carcinogenesis

ABSTRACT: DNA methylation profile in rat bladder carcinogenesis treated with dimethylarsinic acid.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE243372 | GEO | 2023/11/06

REPOSITORIES: GEO

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Aberrant DNA Methylation in Dimethylarsinic Acid-induced Rat Bladder Carcinogenesis

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DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis.

Project description:Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma (UC) induced by dimethylarsinic acid (DMAV), a major organic metabolite of arsenic. We performed genome-wide DNA methylation and microarray gene expression analyses of DMAV-induced rat UCs and the urothelium of rats treated for 4 weeks with DMAV. We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV. We also found that CPXM1 is aberrantly methylated and downregulated in human bladder cancers and human bladder cancer cells. Genes with aberrant DNA methylation and downregulated expression in DMAV-exposed bladder urothelium and in DMAV-induced UCs in rats, suggest that these alterations occurred in the early stages of arsenic-induced bladder carcinogenesis. Further study to evaluate the functions of these genes will advance our understanding of the role of aberrant DNA methylation in arsenic bladder carcinogenesis, and will also facilitate the identification of new therapeutic targets for arsenic-related bladder cancers.

| S-EPMC10648661 | biostudies-literature

Urinary bladder in F344 rats: Control vs dimethylarsinic acid-induced tumors

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Expression data from rat orthotopic bladder cancer

Project description:In the development and progression of bladder cancer, there are many genetic changes. We established a SD rat orthotopic bladder cancer model through intravesical instillation of N-methyl-nitrosourea and pathologic diagnosis is bladder transtional cell carcinomal (BTCC). We used microarrays to analysis the gene expression changes among these rat bladder carcinoma, adjacent normal tissues and bladder tissues of normal rats.

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Lung in neonatal mice: Control vs transplacental treated with dimethylarsinic acid (DMA)

Project description:The gene expression profling between Control and transplacental treated with 200 ppm dimethylarsinic acid (DMA) for 10 days in lung of neonatal male mice.

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Lung in neonatal mice: Control vs. transplacental treated with dimethylarsinic acid (DMA)

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rat bladder LC-MS/MS proteomics

Project description:Objective: Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. Methods: The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Results: Totally 3051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1414 up-regulated and 1637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression of five protein-encoding circRNA were further validated by quantitative RT-PCR and mass spectrometry. Conclusion: The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.

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