Lin Hongyu, Feng Yahui, Liu Hangfeng, Zhang Jinkang, Zhang Xiaolin, Ying Xue, Shi Yuhong, Tan Hao, Tu Wenling
The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, People's Republic of China.
School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, People's Republic of China.
Biologics. 2025 Apr 22;19:231-249. doi: 10.2147/BTT.S496064. eCollection 2025.
Esophageal epithelial cells are essential for esophageal homeostasis and defense against harmful stimuli, but the mechanisms of radiation-induced injury in these cells are poorly understood. The competitive endogenous RNA (ceRNA) network, involved in various physiological processes and diseases, may also play a role in radiation-induced injury, although its mechanism remains unclear. This study aimed to investigate the effects of ionizing radiation on human esophageal epithelial cells and explore the role of the ceRNA network in this injury.
Cellular phenotype experiments assessed the effects of ionizing radiation on human esophageal epithelial cells. Whole transcriptome sequencing (lncRNA, circRNA, miRNA, and mRNA) was performed on cells exposed to 0, 2, and 4 Gy radiation. Differentially expressed RNAs (dd-DERs) were identified through differential expression analysis and dose-dependent screening. A ceRNA network was constructed using co-expression analysis and binding site prediction. Real-time quantitative PCR validated the expression levels of selected dd-DERs, and gene set enrichment analysis explored affected pathways.
We identified 41 lncRNAs, 18 miRNAs, and 192 mRNAs as dose-dependent differentially expressed RNAs. A ceRNA network comprising 10 lncRNAs, 5 miRNAs, and 55 mRNAs was established. Real-time PCR confirmed the expression levels of 8 dd-DERs within the network. Gene set enrichment analysis showed that radiation disrupted channel activity, cell replication, repair, and immune response. Functional enrichment analysis revealed modulation of metabolic pathways, particularly involving UGT1A family members.
This study established a ceRNA network related to radiation-induced esophageal epithelial cell injury, advancing our understanding of its pathophysiology. The ceRNA network may mediate injury through metabolic pathway modulation. Future work should focus on elucidating specific ceRNA interactions and exploring therapeutic potential for mitigating radiation-induced esophageal injury.
食管上皮细胞对于食管内环境稳定及抵御有害刺激至关重要，但这些细胞中辐射诱导损伤的机制尚不清楚。竞争性内源RNA（ceRNA）网络参与多种生理过程和疾病，可能也在辐射诱导损伤中发挥作用，尽管其机制仍不明确。本研究旨在探讨电离辐射对人食管上皮细胞的影响，并探究ceRNA网络在这种损伤中的作用。
细胞表型实验评估电离辐射对人食管上皮细胞的影响。对接受0、2和4 Gy辐射的细胞进行全转录组测序（lncRNA、circRNA、miRNA和mRNA）。通过差异表达分析和剂量依赖性筛选鉴定差异表达RNA（dd-DERs）。利用共表达分析和结合位点预测构建ceRNA网络。实时定量PCR验证所选dd-DERs的表达水平，基因集富集分析探索受影响的通路。
我们鉴定出41种lncRNA、18种miRNA和192种mRNA为剂量依赖性差异表达RNA。建立了一个由10种lncRNA、5种miRNA和55种mRNA组成的ceRNA网络。实时PCR证实了网络内8种dd-DERs的表达水平。基因集富集分析表明，辐射破坏了通道活性、细胞复制、修复和免疫反应。功能富集分析显示代谢途径受到调节，特别是涉及UGT1A家族成员。
本研究建立了与辐射诱导的食管上皮细胞损伤相关的ceRNA网络，增进了我们对其病理生理学的理解。ceRNA网络可能通过调节代谢途径介导损伤。未来的工作应集中在阐明特定的ceRNA相互作用，并探索减轻辐射诱导的食管损伤的治疗潜力。
