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Updated: Jul 5, 2025
In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration
Published on: February 23, 2019
Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with
Mehdi Koushki1, Nasrin Amiri-Dashatan2, Mostafa Rezaei-Tavirani3
1Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Abstract:
Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.
Insights
This study reveals key molecular mechanisms in arsenic-induced skin cancer (cSCC) and identifies protective agents like folic acid and quercetin. These findings offer insights into potential therapeutic strategies against arsenic toxicity.
Area of Science:
- Molecular Biology
- Toxicology
- Dermatology
Background:
- Arsenic exposure is linked to various cancers, including cutaneous squamous cell carcinoma (cSCC).
- Complex molecular mechanisms underlie arsenic-induced malignant transformation.
- Understanding these pathways is crucial for developing preventive strategies.
Purpose of the Study:
- To elucidate molecular mechanisms of arsenic-induced cSCC.
- To identify potential protective factors against arsenic toxicity.
- To explore therapeutic targets for arsenic-related skin cancer.
Main Methods:
- RNA sequencing (RNA-seq) to identify differentially expressed genes in arsenic-exposed keratinocytes.
- Construction of protein-protein interaction (PPI) networks to identify key subnetworks.
- Utilized the Comparative Toxicogenomics Database (CTD) to find protective compounds.
- Molecular docking to assess binding affinity between protective agents and target proteins.
Main Results:
- Identified 15 key proteins in the arsenic-responsive subnetwork critical for cSCC.
- Discovered 7 effective protective agents, including folic acid, quercetin, zinc, and selenium.
- Unfolded protein response pathways were highlighted as major processes.
- Folic acid and quercetin showed significant binding affinity with top genes like FN1, IL1A, and CCN2.
Conclusions:
- The study provides a comprehensive view of molecular mechanisms in arsenic-induced cSCC.
- Identified promising protective agents and potential therapeutic targets.
- Suggests that targeting unfolded protein response pathways may be beneficial in managing arsenic toxicity.
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