TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis

Inhal Toxicol. 2021 Feb;33(3):113-120. doi: 10.1080/08958378.2021.1908461. Epub 2021 Apr 6.

Abstract

Background: Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches.

Methods: High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool.

Results: The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells.

Conclusion: The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.

Keywords: Formaldehyde; bioinformatics; carcinogenesis; environmental pollution; head and neck carcinoma.

MeSH terms

  • Amphiregulin / genetics
  • Amphiregulin / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism*
  • Computer Simulation
  • Formaldehyde / toxicity*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Head and Neck Neoplasms / chemically induced*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Models, Biological
  • Protein Interaction Maps

Substances

  • AREG protein, human
  • Amphiregulin
  • CXCL1 protein, human
  • Carrier Proteins
  • Chemokine CXCL1
  • TXNIP protein, human
  • Formaldehyde