Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study
Artikel i vetenskaplig tidskrift, 2024

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.

Skin carcinogenesis

Unfolded protein response

Arsenic

Protective agents

Molecular docking

Toxicogenomic

Författare

Mehdi Koushki

School of Medicine, Zanjan University of Medical Sciences (ZUMS)

Nasrin Amiri-Dashatan

Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences (ZUMS)

Mostafa Rezaei-Tavirani

SBUMS Proteomics Research Center

Reza M. Robati

Skin Research Center, Shahid Beheshti University of Medical Sciences

Loghman Hakim Educational Hospital

Fatemeh Fateminasab

University of Mazandaran

Shadi Rahimi

Chalmers, Life sciences, Systembiologi

Zahra Razzaghi

Laser Application in Medical Sciences Research Center

Masoumeh Farahani

Skin Research Center, Shahid Beheshti University of Medical Sciences

Food and Chemical Toxicology

0278-6915 (ISSN) 18736351 (eISSN)

Vol. 185 114451

Ämneskategorier

Biokemi och molekylärbiologi

Cancer och onkologi

DOI

10.1016/j.fct.2024.114451

PubMed

38219847

Mer information

Senast uppdaterat

2024-02-02