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A Comprehensive Transcriptomic Analysis of Arsenic-Induced Bladder Carcinogenesis.
Vaibhav Shukla1, Balaji Chandrasekaran1, Ashish Tyagi1
1Rangel College of Pharmacy, Texas A&M University, College Station, TX 77843, USA.
Cells
|August 12, 2022
Summary
Arsenic exposure promotes bladder cancer by altering cell signaling pathways and inducing stem cell activators. This reprogramming of normal bladder cells into cancer stem cells drives malignant transformation.
Area of Science:
- Environmental Toxicology
- Cancer Biology
- Molecular Carcinogenesis
Background:
- Arsenic is a known carcinogen linked to bladder cancer.
- The precise molecular mechanisms of arsenic-induced bladder carcinogenesis are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying arsenic-induced bladder cancer.
- To identify key pathways and genes involved in arsenic's carcinogenic effects on bladder epithelial cells.
Main Methods:
- Normal bladder epithelial cells (TRT-HU1) were exposed to physiological arsenic concentrations (250 nM) for over 12 months.
- Differential gene expression (DEG) analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed.
- Quantitative PCR (qPCR) was used to validate transcriptomic findings.
Main Results:
- Arsenic exposure led to increased cell proliferation and colony formation from 4 months onwards.
- Significant deregulation of 1558 and 1943 genes was observed at 6 and 12 months, respectively.
- Key cell proliferation and survival pathways (MAPK, PI3K/AKT, Hippo) were altered, with significant enrichment of stem cell activators (ALDH1A1, HNF1b, MAL, NR1H4, CDH1).
Conclusions:
- Arsenic exposure induces a survival advantage in bladder epithelial cells through stem cell activators.
- These stem cell activators facilitate the reprogramming of normal cells into a cancer stem cell phenotype.
- This reprogramming is a critical step in arsenic-induced malignant transformation of bladder cells.
