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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Radiation Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1600597

Potential Protective Regulatory Effects on Radiation-Induced Esophageal Injury in TUT4⁻ / ⁻ Mice

Provisionally accepted
Huiwen  RenHuiwen Ren1,2*Wei  LiWei Li3Jianlin  WangJianlin Wang4Zhiqiang  SunZhiqiang Sun4Renhua  HuangRenhua Huang5Judong  LuoJudong Luo6Bo  GaoBo Gao7
  • 1Graduate School of Dalian Medical University, Dalian, China
  • 2Department of Oncology, Jining First People's Hospital, Jining, China
  • 3Shanghai Tenth People's Hospital, Tongji University, Shanghai, Shanghai Municipality, China
  • 4Department of Radiation Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
  • 5Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 6Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 7The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, China., Changzhou, China

The final, formatted version of the article will be published soon.

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 radiationinduced esophageal injury remains poorly understood. 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. 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.

Keywords: Esophageal tissue, radioprotection, TUT4, radiation-induced esophageal injury, radioactivity

Received: 26 Mar 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 Ren, Li, Wang, Sun, Huang, Luo and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Huiwen Ren, Graduate School of Dalian Medical University, Dalian, China

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