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Updated: Jan 18, 2026
Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
Potential protective regulatory effects on radiation-induced esophageal injury in TUT4-/- mice
Huiwen Ren1, Wei Li2, Zhigang Fan3
1Department of Radiotherapy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Introduction:
Terminal uridyl transferase 4 (TUT4), a nucleotide transferase that modifies miRNA sequences, plays a critical role in regulating miRNA target interactions and function. However, its involvement in radiation-induced esophageal injury remains poorly understood.
Methods:
To investigate this, we performed computational analysis of RNA-seq data from irradiated esophageal tissues of wild-type and TUT4-knockout (TUT4-/-) mice, identifying 53 differentially expressed mRNAs (DEmRNAs), of which 30 were upregulated and 23 downregulated.
Results:
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these DEmRNAs were significantly associated with biological processes including lipid metabolism, fatty acid metabolism, proteolysis, and broader metabolic functions. Notably, DEmRNAs in TUT4-/- esophageal tissues showed marked enrichment in the renin-angiotensin system and peroxisome proliferator-activated receptor signaling pathways, implicating their potential roles in the pathogenesis of radiation-induced esophageal injury. In addition, we identified a regulatory axis in which a long non-coding RNA competes with miR-182 to modulate the competing endogenous RNA network governing TUT4 target genes. Collectively, our transcriptomic analysis offers novel mechanistic insights into how TUT4 may confer protection against radiation-induced damage in esophageal tissues.
Insights
Terminal uridyl transferase 4 (TUT4) influences radiation-induced esophageal injury by regulating gene expression. Loss of TUT4 impacts metabolic pathways and signaling, suggesting a protective role against radiation damage.
Area of Science:
- Molecular Biology
- Genomics
- Radiation Oncology
Background:
- Terminal uridyl transferase 4 (TUT4) is a key regulator of microRNA (miRNA) modification and function.
- The role of TUT4 in radiation-induced esophageal injury is not well understood.
Purpose of the Study:
- To investigate the role of TUT4 in the molecular mechanisms underlying radiation-induced esophageal injury.
- To identify genes and pathways regulated by TUT4 in response to radiation exposure.
Main Methods:
- Computational analysis of RNA-sequencing data from irradiated wild-type and TUT4-knockout mouse esophageal tissues.
- Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses to identify differentially expressed mRNAs (DEmRNAs) and associated pathways.
Main Results:
- Identified 53 DEmRNAs, with 30 upregulated and 23 downregulated in irradiated esophageal tissues.
- DEmRNAs were enriched in lipid metabolism, fatty acid metabolism, and proteolysis pathways.
- TUT4-knockout tissues showed enrichment in the renin-angiotensin system and PPAR signaling pathways, suggesting roles in injury pathogenesis.
- Discovered a regulatory axis involving lncRNA, miR-182, and competing endogenous RNA networks affecting TUT4 targets.
Conclusions:
- Transcriptomic analysis provides novel insights into TUT4's protective mechanisms against radiation-induced esophageal damage.
- TUT4 influences key metabolic and signaling pathways involved in radiation injury.
- The identified regulatory network highlights potential therapeutic targets for mitigating esophageal injury.
