Potential mechanisms of radiation-induced esophageal tissue injury in TUT4 -/- mice

Abstract Background Radiation-induced esophageal injury remains a limitation of radiotherapy for lung and esophageal cancer patients. Esophageal epithelial cells are extremely sensitive to irradiation; nevertheless, factors involved in the radiosensitivity of esophageal epithelial cells are still unknown. Terminal uridyl transferase 4 (TUT4) can modify the sequence of miRNAs, which affects their regulation of miRNA targets and function. Methods In this study, we used transcriptome sequencing technology to identify mRNAs that were differentially expressed before and after radiotherapy in esophageal epithelial cells. Results We further explored the mRNA expression profiles between wild-type and TUT4 knockout esophageal epithelial tissue. Volcano and heatmap plot unsupervised hierarchical clustering analyses were performed to classify the samples. Enrichment analysis of Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Annotation of differential genes from metabolism, genetic information processing, environmental information processing, cellular processes and organismal systems human diseases was conducted. Conclusions The aberrantly expressed genes were significantly enriched in irradiation-related biological processes, such as lipid metabolic process, fatty acid metabolic process, proteolysis, and metabolic process. Moreover, we explored the distribution of the transcription factor family and its target genes among the differentially expressed genes. In addition, we found that PPAR pathway and the renin-angiotensin pathway might serve as therapeutic targets in TUT4-related radiation-induced esophageal injury.