Ren Huiwen, Li Wei, Fan Zhigang, Wang Jianlin, Sun Zhiqiang, Huang Renhua, Luo Judong, Gao Bo
Department of Radiotherapy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Clinical Nutrition Department of The Tenth People's Hospital, Tongji University, Shanghai, China.
Front Oncol. 2025 Aug 26;15:1600597. doi: 10.3389/fonc.2025.1600597. eCollection 2025.
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.
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.
末端尿苷酰转移酶4（TUT4）是一种修饰miRNA序列的核苷酸转移酶，在调节miRNA靶标相互作用和功能方面发挥着关键作用。然而，其在辐射诱导的食管损伤中的作用仍知之甚少。
为了研究这一问题，我们对野生型和TUT4基因敲除（TUT4-/-）小鼠受辐射食管组织的RNA测序数据进行了计算分析，鉴定出53个差异表达的mRNA（DEmRNA），其中30个上调，23个下调。
基因本体论和京都基因与基因组百科全书富集分析表明，这些DEmRNA与脂质代谢、脂肪酸代谢、蛋白水解和更广泛的代谢功能等生物学过程显著相关。值得注意的是，TUT4-/-食管组织中的DEmRNA在肾素-血管紧张素系统和过氧化物酶体增殖物激活受体信号通路中表现出明显富集，暗示它们在辐射诱导的食管损伤发病机制中的潜在作用。此外，我们鉴定出一个调控轴，其中一个长链非编码RNA与miR-182竞争，以调节控制TUT4靶基因的竞争性内源RNA网络。总体而言，我们的转录组分析为TUT4如何保护食管组织免受辐射诱导的损伤提供了新的机制见解。
