Screening of potential genes and transcription factors involved in post-radiation cognitive dysfunction in mice via bioinformatics

Transl Cancer Res. 2020 Oct;9(10):6383-6391. doi: 10.21037/tcr-20-1767.

Abstract

Background: This study aimed to identify potential genes and transcription factors involved in postradiation cognitive dysfunction using bioinformatics analysis.

Methods: Bioinformatics tools were used to identify differentially expressed mRNAs between postradiation cognitive dysfunctional and control tissue. The GSE115735 dataset containing mRNA expression profiles was downloaded from the Gene Expression Omnibus database. The mRNA expression data corresponded to three hippocampus and three brain lateral ventricles from postradiation cognitive dysfunctional mice and controls. The differentially expressed mRNAs between the two groups were identified, and protein-protein interaction network was constructed. This was followed by functional enrichment and pathway analysis with further prediction of transcription factors that targeted differentially expressed mRNAs. Network analysis was conducted between the differentially expressed mRNAs and these potential transcription factors.

Results: A total of 134 differentially expressed mRNAs were obtained, including 64 mRNAs in the hippocampus and 84 in the posterior lateral ventricles. Fourteen mRNAs were expressed differentially in both tissues. Furthermore, genes in the network were strongly enriched in neuroactive ligand-receptor interactions, regulation of calcium ion transport, mitotic spindle associated pathway, and TGF-beta signaling pathways. Six transcription factors associated with the regulation of target genes were identified.

Conclusions: Most of the genes identified were involved in transcriptional regulation, including TFAP4, RUNX1, and CUX2, which may play important roles in the development of postradiation cognitive dysfunction.

Keywords: Biological ontologies; central nervous system (CNS); cognitive dissonance; genetic; radiotherapy; transcription.