空间辐射与微重力通过β-arrestin1-FN1-YAP通路协同诱导肿瘤发生的机理研究

对于长周期深空探索任务而言，空间辐射诱导的肿瘤发生是航天员面临的主要健康风险之一。空间辐射生物学效应往往受到微重力等其它空间环境因素的影响，然而，微重力在空间辐射诱导的肿瘤发生中发挥何种作用迄今未见报道。我们前期研究发现，α粒子辐射协同模拟微重力诱导肺上皮细胞中β-arrestin1入核、下游FN1（Fibronectin1）表达上调及YAP（Yes-associated protein）转录活性升高，而YAP已被证明在多种肿瘤发生中发挥重要作用。因此，我们推测辐射协同微重力诱导肿瘤发生。本项目基于前期研究基础，拟从分子、细胞及动物水平上深入研究微重力对空间辐射诱导的肺上皮细胞恶性转化和肿瘤发生的影响及β-arrestin1-FN1-YAP通路在其中的作用机制。该项研究有助于明确微重力对空间辐射致癌效应的影响及其机制，对于准确评估空间辐射致癌风险并开发有效防护措施具有重要意义。

Space radiation-induced tumorigenesis is one of the major health risks to astronauts on long-duration deep space exploration missions. The biological effects of space radiation are often influenced by other space environmental factors, such as microgravity. However, whether microgravity plays a role in space radiation-induced tumorigenesis and what role it plays have not been reported so far. In our previous studies, β-arrestin1 was found to be induced to translocate into nucleus in human lung epithelial cells by both α particle irradiation and simulated microgravity synergistically. Moreover, it was found that α particle irradiation synergized with simulated microgravity to enhance the expression of downstream Fibronectin1 (FN1) and transcriptional activity of Yes-associated protein (YAP), while YAP has been shown to play an important role in the tumorigenesis of a variety of tumors. Thus we speculate that radiation synergized with microgravity to induce tumorigenesis. Based on the previous findings, this project is proposed to study the effects of simulated microgravity on space radiation-induced malignant transformation and tumorigenesis of human lung epithelial cells as well as the underlying mechanisms mediated by β-arrestin1-FN1-YAP pathway at molecular, cellular and animal levels. This study will help to clarify the effects of microgravity on space radiation-induced tumorigenesis and the underlying molecular mechanisms. Besides, it will be of great significance to accurately assess the risk of space radiation-induced tumorigenesis and to develop effective countermeasures.