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. 2022 Oct 27;20(4):15593258221136810.
doi: 10.1177/15593258221136810. eCollection 2022 Oct-Dec.

Differentially Expressed mRNAs and Potential Mechanisms of Radiation-Induced TUT4-/- Esophageal Cell Injury

Zhiqiang Sun  1   2 , Jiaqi Zhang  3 , Fanye Zeng  4 , Shuyu Zhang  1   2 , Zhifang Chai  1   2 , Judong Luo  3 , Jianping Cao  1   2
Affiliations

Differentially Expressed mRNAs and Potential Mechanisms of Radiation-Induced TUT4-/- Esophageal Cell Injury

Zhiqiang Sun et al. Dose Response. .

Abstract

Radiation-induced esophageal injury remains a limitation for the process 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) could modify the sequence of miRNAs, which affect their regulation on miRNA targets and function. In this study, we used transcriptome sequencing technology to identify mRNAs that were differentially expressed before and after radiotherapy in esophageal epithelial cells. We further explored the mRNA expression profiles between wild-type and TUT4 knockout esophageal epithelial cells. Volcano and heatmap plots unsupervised hierarchical clustering analysis were performed to classify the samples. Enrichment analysis on Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathways was performed. We annotated differential genes from metabolism, genetic information processing, environmental information processing, cellular processes, and organismal systems human diseases. The aberrantly expressed genes are significantly enriched in irradiation-related biological processes, such as DNA replication, ferroptosis, and cell cycle. Moreover, we explored the distribution of transcription factor family and its target genes in differential genes. These mRNAs might serve as therapeutic targets in TUT4-related radiation-induced esophageal injury.

Keywords: esophageal epithelial; radiation-induced esophageal injury; radiosensitivity; terminal uridyl transferase 4.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Gene expression level, principal component analysis, and correlations among samples. (A) A box plot shows the distribution of expression data from all the samples. (B) Principal component analysis (PCA). (C) The correlations among samples were analyzed by Pearson correlation. (D) The gene expression cluster diagram of samples. Group A: TUT4−/− nonirradiated group, Group B: TUT4 +/+ nonirradiation group, Group C: TUT4−/− irradiation group, Group D: TUT4 +/+ irradiation group.
Figure 2.
Figure 2.
Expression profiles of radiotherapy-related DEGs and enrichment analysis. (A) Volcano map of DEG expression levels between the irradiated group (Group D) and nonirradiated group (Group B). (B) Heatmap hierarchical clustering analysis of DEGs in the irradiation group and nonirradiated group. (C) GO enrichment analysis of DEGs showed biological process (BP); cellular component (CC); molecular function (MF); (D) KEGG pathway classification of DEGs. (E) KEGG enrichment analysis of DEGs.
Figure 3.
Figure 3.
KEGG pathway diagram, and statistics of transcription factors family and target genes. (A and B) Malaria and cell adhesion molecules pathway diagram. Red nodes are associated with up-regulated genes, and duck green nodes are associated with down-regulated genes. (C) Transcription factors distribution of DEGs. (D) Target genes statistics of DEGs.
Figure 4.
Figure 4.
Expression profiles of TUT4−/− radiotherapy-related DEGs and enrichment analysis. (A) Volcano map of DEG expression levels between the TUT4−/− irradiation group and TUT4−/− nonirradiated group. (B) Heatmap hierarchical clustering analysis of TUT4−/− DEGs in the irradiation group and nonirradiated group. (C) GO enrichment analysis of TUT4−/− DEGs showed biological process (BP); cellular component (CC); molecular function (MF); (D) KEGG pathway classification of DEGs. (E) KEGG enrichment analysis of TUT4−/− DEGs.
Figure 5.
Figure 5.
KEGG pathway diagram, and statistics of transcription factors family and target genes between the TUT4−/− irradiation group and TUT4−/− nonirradiated group. (A and B) DNA replication and ferroptosis pathway diagram. (C) Transcription factors distribution of TUT4−/− DEGs. (D) Target genes statistics of TUT4−/− DEGs.
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