Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice

IntroductionTerminal 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.MethodsTo investigate this,...

Full description

Saved in:
Bibliographic Details
Main Authors: Huiwen Ren, Wei Li, Zhigang Fan, Jianlin Wang, Zhiqiang Sun, Renhua Huang, Judong Luo, Bo Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1600597/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849222601077948416
author Huiwen Ren
Wei Li
Zhigang Fan
Jianlin Wang
Zhiqiang Sun
Renhua Huang
Judong Luo
Bo Gao
author_facet Huiwen Ren
Wei Li
Zhigang Fan
Jianlin Wang
Zhiqiang Sun
Renhua Huang
Judong Luo
Bo Gao
author_sort Huiwen Ren
collection DOAJ
description IntroductionTerminal 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.MethodsTo 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.ResultsGene 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.
format Article
id doaj-art-27efa69bd00a4a108124e2b608f1150a
institution Kabale University
issn 2234-943X
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-27efa69bd00a4a108124e2b608f1150a2025-08-26T04:12:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16005971600597Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− miceHuiwen Ren0Wei Li1Zhigang Fan2Jianlin Wang3Zhiqiang Sun4Renhua Huang5Judong Luo6Bo Gao7Department of Radiotherapy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaClinical Nutrition Department of The Tenth People’s Hospital, Tongji University, Shanghai, ChinaDepartment of Oncology, 3201 Hospital of Xi’an Jiaotong University Health Science Center, Shanghai, ChinaDepartment of Radiotherapy, The Second People’s Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, ChinaDepartment of Radiotherapy, The Second People’s Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, ChinaDepartment of Radiation, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Radiotherapy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Rheumatology and Immunology, The Second People's Hospital of Changzhou, the Third Affilitated Hosptial of Nanjing Medical University, Changzhou, ChinaIntroductionTerminal 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.MethodsTo 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.ResultsGene 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1600597/fullesophageal tissueradioprotectionTUT4radiation-induced esophageal injuryradioactivity
spellingShingle Huiwen Ren
Wei Li
Zhigang Fan
Jianlin Wang
Zhiqiang Sun
Renhua Huang
Judong Luo
Bo Gao
Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
Frontiers in Oncology
esophageal tissue
radioprotection
TUT4
radiation-induced esophageal injury
radioactivity
title Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
title_full Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
title_fullStr Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
title_full_unstemmed Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
title_short Potential protective regulatory effects on radiation−induced esophageal injury in TUT4−/− mice
title_sort potential protective regulatory effects on radiation induced esophageal injury in tut4 mice
topic esophageal tissue
radioprotection
TUT4
radiation-induced esophageal injury
radioactivity
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1600597/full
work_keys_str_mv AT huiwenren potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT weili potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT zhigangfan potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT jianlinwang potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT zhiqiangsun potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT renhuahuang potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT judongluo potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice
AT bogao potentialprotectiveregulatoryeffectsonradiationinducedesophagealinjuryintut4mice