Derepression of retrotransposable elements in the development of radiation-induced late effects: advancements and perspective

Yawen WEN; Li SUN; Xiangpeng ZHENG

doi:10.19401/j.cnki.1007-3639.2025.08.010

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Derepression of retrotransposable elements in the development of radiation-induced late effects: advancements and perspective

Review | 更新时间：2025-12-31

- Derepression of retrotransposable elements in the development of radiation-induced late effects: advancements and perspective
- China Oncology Vol. 35, Issue 8, Pages: 808-814(2025)
- 作者机构：
  
  复旦大学附属华东医院肿瘤放疗科，上海 200040
- 作者简介：
- 基金信息：
  
  Shanghai Anti-Cancer Association “Eagle Plan”(SACA-CY24A03)
- DOI：10.19401/j.cnki.1007-3639.2025.08.010
  CLC： R730.55
- Received：13 March 2025，
  
  Revised：2025-06-11，
  
  Published：30 August 2025
- 稿件说明：
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Yawen WEN, Li SUN, Xiangpeng ZHENG. Derepression of retrotransposable elements in the development of radiation-induced late effects: advancements and perspective[J]. China Oncology, 2025, 35(8): 808-814.
DOI：

Yawen WEN, Li SUN, Xiangpeng ZHENG. Derepression of retrotransposable elements in the development of radiation-induced late effects: advancements and perspective[J]. China Oncology, 2025, 35(8): 808-814. DOI： 10.19401/j.cnki.1007-3639.2025.08.010.

摘要

放疗导致晚反应或延迟反应对患者的长期生活质量影响甚大，然而目前对其发生和发展机制的认识非常有限，缺乏有效的风险预测方法和预防干预措施。基于放射生物学和放疗诱导衰老模型的研究提示，放疗能够改变晚反应组织细胞内的表观遗传学特征，诱发逆转座元件序列（特别是内源性逆转录病毒元件）的表达活化，进而触发细胞质内的异常核酸感受器系统（cGAS-STING和MDA5/RIG-I-MAVS）和Ⅰ型干扰素介导的免疫炎症反应。本文对相关研究结果进行综述，认为“放疗-表观遗传学改变-逆转座元件活化”诱导的自身免疫样炎症反应是放疗晚反应发生的不可忽视的机制基础，通过构建基于表观遗传学特征和细胞类型与放疗剂量的晚反应风险模型和发展靶向表观遗传学抑制逆转座元件表达有助于预防或减轻放疗晚反应。

Abstract

Radiotherapy-induced late effects (RILE) or delayed reactions have significant impacts on patients' long-term quality of life. However

current understanding of their developmental mechanisms remains limited

with a lack of effective risk prediction models and preventive interventions. Radiobiological studies and radiation-induced senescence models have revealed that radiotherapy can alter the epigenetic characteristics in late-responding tissue cells

leading to derepression of retrotransposable elements (particularly endogenous retroviral elements)

subsequent activation of cytoplasmic nucleic acid sensor systems (cGAS-STING

MDA5/RIG-I-MAVS) and type Ⅰ interferon-mediated immune-inflammatory responses. This review summarized relevant research findings

proposing that the autoimmune-like inflammatory response induced by the 'radiotherapy-epigenetic alteration-retrotransposable element activation’ cascade is an underinvestigated mechanistic basis in the development of RILE. Constructing risk prediction models for late effects based on epigenetic signatures

cell type

and radiation dose

along with developing strategies to epigenetically suppress retrotransposable element expression

holds promise for preventing or mitigating RILE.

关键词

Keywords

references

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