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Updated: Jul 11, 2025
Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors
Published on: March 29, 2019
Gene expression profiles to analyze the anticancer and carcinogenic effects of arsenic in bladder cancer
Xiaomin Han1,2,3, Tengteng Zhang3, Qiang Ma3
1Department of Oncology and Chemistry, The First Affiliated Hospital, Jinan University Guangzhou 510632, Guangdong, China.
Objectives:
Arsenic is one of the greatest hazards as an environmental carcinogen. At the same time it is also a promising anticancer agent, that can be used to treat acute promyelocytic leukemia (APL) and some other tumors. Arsenic trioxide (ATO) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells. However, the molecular mechanisms that govern these paradoxical effects of arsenic in bladder cancer remain unclear. We speculate that they share the common mechanism that arsenic binds to the target proteins and subsequently impacts the expression of downstream genes.
Methods:
To address this issue, three Gene Set Enrichments (GSE) were loaded from the Gene Expression Omnibus (GEO) database with four expression matrices. Three of them were mice samples at exposure times of 1, 2, and 12 weeks, and the last was a human urothelial cell (HUC1) sample. Differentially expressed genes (DEGs) from 4 expression groups were identified at iDEP and analyzed at Metascape and Cytoscape for signaling pathway analysis and protein-protein interaction (PPI) analysis. The web-portals UALCAN and GEPIA were used to analyze the role of DEGs in the crosstalk between carcinogenic and anticancer effects. The putative downstream genes of arsenic binding proteins were retrieved using the Cistrome Data Browser. Real-time PCR was used to validate the expression of DEGs.
Results:
The signaling pathways referred to lipid metabolism. Responses to various stimuli or hormones were overrepresented in 4 expression matrices. The PPI network emphasized the role of KRAS and TNF signaling in different groups. Furthermore, BDKRB2, FOS, NR4A1, PLAU, SH3BGRL, and F10 played an important role in the crosstalk between carcinogenic and anticancer effects in bladder cancer. Arsenic may impact the activity of ACTB, BACH1, NME2, RBBP4, PARP1, and PML by direct binding, and thus influence the expression of downstream genes such as PAX6, MLLT11, LTBP1, PCSK5, ZFP36, COL8A2, and IL1R2.
Conclusion:
Arsenic exerted carcinogenic and anticancer functions by altering the expression of crosstalk genes such as BDKRB2, FOS, NR4A1, PLAU, SH3BGRL, and F10, and these were due to arsenic binding proteins.
Insights
Arsenic exhibits dual roles as a carcinogen and anticancer agent. This study reveals arsenic alters gene expression in bladder cancer by binding to proteins, influencing both carcinogenic and therapeutic effects.
Area of Science:
- Environmental Health
- Oncology
- Molecular Biology
Background:
- Arsenic is a known environmental carcinogen with paradoxical anticancer properties, notably in treating acute promyelocytic leukemia (APL).
- The precise molecular mechanisms underlying arsenic's dual role in bladder cancer remain unclear.
- Arsenic trioxide (ATO) functions by degrading oncogenic proteins in APL, suggesting a protein-binding mechanism.
Purpose of the Study:
- To elucidate the molecular mechanisms of arsenic's paradoxical carcinogenic and anticancer effects in bladder cancer.
- To identify key genes and signaling pathways involved in arsenic's dual action.
- To investigate the role of arsenic-protein interactions in modulating gene expression.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets from mouse and human urothelial cells (HUC1).
- Identified differentially expressed genes (DEGs) using iDEP and analyzed pathways and protein-protein interactions (PPI) with Metascape and Cytoscape.
- Validated DEGs using real-time PCR and analyzed gene roles in crosstalk using UALCAN and GEPIA.
Main Results:
- Signaling pathways related to lipid metabolism and responses to stimuli were overrepresented.
- KRAS and TNF signaling pathways were highlighted in the PPI network.
- Identified key crosstalk genes (e.g., BDKRB2, FOS, NR4A1) and potential arsenic-binding proteins (e.g., ACTB, BACH1) influencing downstream gene expression.
Conclusions:
- Arsenic's carcinogenic and anticancer functions in bladder cancer are mediated by altering the expression of specific crosstalk genes.
- These alterations are a consequence of arsenic binding to target proteins, impacting downstream gene expression.
- Understanding these mechanisms offers insights into arsenic's complex role in cancer biology.
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