Comparative Transcriptomic Analysis Unveils Divergent Effects of FLASH Versus Conventional Irradiation on Skin Cells.

IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Dose-Response Pub Date : 2025-05-20 eCollection Date: 2025-04-01 DOI:10.1177/15593258251342837
Mengmeng Xu, Qiliang Peng, Jun Zhang, Zhiming Xu, Xinyang Cheng, Zhifei Cao, Yongsheng Zhang
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引用次数: 0

Abstract

Objectives: FLASH radiotherapy is garnering attention for its capacity to diminish skin toxicity without compromising tumoricidal efficacy, presenting a stark contrast to conventional (CONV) radiotherapy. Despite its promise, the underlying molecular mechanisms of FLASH irradiation (FLASH-IR) on skin are not yet fully elucidated.

Methods: This study investigated the transcriptomic responses of human foreskin fibroblast cells (HFF-1) via the FLASH-IR or CONV irradiation (CONV-IR), employing the next-generation RNA sequencing (RNA-seq) to capture the gene expression profiles. Our comparative analysis aimed to dissect the cellular and molecular pathways influenced by these two irradiation methods.

Results: We identified a spectrum of differentially expressed genes (DEGs), signaling pathways, and transcriptional networks that were either shared or divergent between FLASH-IR and CONV-IR. Particularly, transcription factor NR4A1 showed significant upregulation in response to FLASH-IR, while chromatin stability factor ELF3 was markedly downregulated following CONV-IR. The top 10 up-regulated DEGs were subjected to qPCR validation, confirming their differential expression in response to FLASH-IR and CONV-IR.

Conclusion: Collectively, our findings delineate unique regulatory landscapes of FLASH-IR and CONV-IR on skin cells, corroborating established effects and shedding new light on the molecular interplay within the context of ultra-high dose radiation.

比较转录组学分析揭示了FLASH与传统照射对皮肤细胞的不同影响。
目的:FLASH放疗因其在不影响杀瘤效果的情况下降低皮肤毒性的能力而受到关注,与传统(CONV)放疗形成鲜明对比。尽管FLASH辐照(FLASH- ir)对皮肤的潜在分子机制尚未完全阐明。方法:本研究通过FLASH-IR或CONV辐照(convr - ir)研究人包皮成纤维细胞(HFF-1)的转录组反应,采用下一代RNA测序(RNA-seq)技术捕获基因表达谱。我们的比较分析旨在剖析受这两种辐照方法影响的细胞和分子途径。结果:我们确定了FLASH-IR和convr - ir之间共享或不同的差异表达基因(DEGs)、信号通路和转录网络的谱。其中,转录因子NR4A1在FLASH-IR下显著上调,而染色质稳定因子ELF3在con - ir下显著下调。对前10个上调的deg进行qPCR验证,确认其在FLASH-IR和convr - ir下的差异表达。结论:总的来说,我们的研究结果描绘了FLASH-IR和convr - ir对皮肤细胞的独特调节景观,证实了既定的影响,并为超高剂量辐射背景下的分子相互作用提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Dose-Response
Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
CiteScore
4.90
自引率
4.00%
发文量
140
审稿时长
>12 weeks
期刊介绍: Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.
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