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河马/Yes相关蛋白信号通路在辐射诱导的胶质瘤细胞凋亡中的作用。

Role of Hippo/YAP signaling in irradiation-induced glioma cell apoptosis.

作者信息

Xu Xiaofei, Chen Yan, Wang Xi, Mu Xingguo

机构信息

Department of Radiology, The Second Hospital of Jilin University, Chang Chun 130041, People's Republic of China.

Department of Neurosurgery, The Second Hospital of Jilin University, Chang Chun 130041, People's Republic of China.

出版信息

Cancer Manag Res. 2019 Aug 9;11:7577-7585. doi: 10.2147/CMAR.S210825. eCollection 2019.

DOI:10.2147/CMAR.S210825
PMID:31496812
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6693089/
Abstract

BACKGROUND

Although Hippo/Yes-associated protein (YAP) signaling plays crucial roles in radiation sensitivity and resistance of multiple kinds of cancers, its role in the radiation sensitivity of glioma cells remains unclear. The present study aimed to reveal Hippo/YAP role in the radiation sensitivity of glioma cells.

METHODS

Glioma U251 cells were administrated with different doses of irradiation. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were used to assess cell viability and apoptosis. Co-immunoprecipitation (co-IP) assay was used to assess the interactions between proteins.

RESULTS

The results showed that irradiation exposure significantly inhibited cell viability and induced cell apoptosis in a dose-dependent manner, as well as decreased YAP1 expression via enhancing RCHY1-mediated YAP1 protein degradation. In addition, we observed that downregulation of YAP1 or RCHY1 weakened the role of irradiation exposure in cell viability inhibition and apoptosis promotion.

CONCLUSION

Collectively, this study emphasizes the vital role of Hippo/YAP signaling in radiation sensitivity of glioma, that RCHY1-mediated YAP1 protein downregulation is a main mechanism accounting for radiation-induced glioma cell apoptosis. Our study may enrich the theoretical basis of Hippo/YAP signaling as a new target for improving radiation sensitivity in glioma.

摘要

背景

尽管Hippo/Yes相关蛋白（YAP）信号通路在多种癌症的辐射敏感性和抗性中发挥着关键作用，但其在胶质瘤细胞辐射敏感性中的作用仍不清楚。本研究旨在揭示Hippo/YAP在胶质瘤细胞辐射敏感性中的作用。

方法

用不同剂量的辐射处理胶质瘤U251细胞。采用细胞计数试剂盒-8（CCK-8）和流式细胞术检测细胞活力和凋亡情况。采用免疫共沉淀（co-IP）试验评估蛋白质之间的相互作用。

结果

结果表明，辐射暴露以剂量依赖性方式显著抑制细胞活力并诱导细胞凋亡，同时通过增强RCHY1介导的YAP1蛋白降解降低YAP1表达。此外，我们观察到YAP1或RCHY1的下调削弱了辐射暴露对细胞活力抑制和凋亡促进的作用。

结论

总体而言，本研究强调了Hippo/YAP信号通路在胶质瘤辐射敏感性中的重要作用，即RCHY1介导的YAP1蛋白下调是辐射诱导胶质瘤细胞凋亡的主要机制。我们的研究可能丰富Hippo/YAP信号通路作为提高胶质瘤辐射敏感性新靶点的理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/c806915130d6/CMAR-11-7577-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/2d37945644be/CMAR-11-7577-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/1069885aaa8b/CMAR-11-7577-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/6b62810ec5cc/CMAR-11-7577-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/c3f60f675d04/CMAR-11-7577-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/b748d3c675b6/CMAR-11-7577-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/c806915130d6/CMAR-11-7577-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/2d37945644be/CMAR-11-7577-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/1069885aaa8b/CMAR-11-7577-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/6b62810ec5cc/CMAR-11-7577-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/c3f60f675d04/CMAR-11-7577-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/b748d3c675b6/CMAR-11-7577-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/6693089/c806915130d6/CMAR-11-7577-g0006.jpg

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