Elucidation of molecular mechanisms, pathways, and diseases modulated by arsenicals through toxogenomics and multi-omics analysis.

Autor: Zargar S; Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: szargar@ksu.edu.sa., Altwaijry N; Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Alanazi H; Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Alshammari AH; Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Alkahtani HM; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Wani TA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: twani@ksu.edu.sa.
Jazyk: angličtina
Zdroj: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2024 Dec; Vol. 86, pp. 127561. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1016/j.jtemb.2024.127561
Abstrakt: Arsenic compounds exist in inorganic and organic forms with inorganic form confirmed as a potent carcinogen. Toxogenomics and multi-omics analysis were used to explore the molecular mechanisms of carcinogenecity induced by arsenicals. Comparative toxogenomics revealed sodium arsenite and arsenate as the most toxic arsenicals to humans, interacting with various genes and altering gene expression through mRNA binding proteins. Both metalloids were classified as Class II toxins by the ProTox II prediction tool, with a lethal dose (LD50) of 149 mg/kg body weight. The most frequently interacting genes were HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM. Analysis of TCGA pan-cancer data revealed that 46 % of hepatocellular carcinoma patients exhibited alterations in the genes HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM, suggesting their significant role in the development of this disease. The alteration in the gene list decreased the overall patient survival but insignificantly in the Kaplan-Meier curves revealing insignificant role in survival. GSEA suggested significant enrichment of the gene list in pathways involved in the G2M checkpoint, apoptosis, hypoxia, TNFA signaling via NFKB, PI3K AKTMTOR signaling, P53, IFN gamma and inflammatory response pathways revealing the involvement of these pathways. Ten microRNAs (miRNAs) regulated the expressions of the genes involved in the above-mentioned pathways with the significant enrichment in miR-21-3p, miR-206 and mir486a-5p. The relevant pathway and graphical representation of the network of miRNA-target interactions identified by the enrichment analysis along with disease ontologies were predicted. This study will be helpful insight into setting of laboratory experiments.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seema zargar reports financial support was provided by King Saud University.
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Databáze: MEDLINE
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