Departments of Geriatrics and Oncology, Guangzhou Geriatric Hospital, 510180, Guangzhou, China.
Departments of Geriatrics and Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, 510180, Guangzhou, China.
Cell Death Dis. 2021 Jul 21;12(8):724. doi: 10.1038/s41419-021-04000-3.
Glioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，放射治疗在其治疗管理中起着关键作用。不幸的是，放射抗性的发展是普遍存在的。在这里，我们利用全基因组 CRISPR 激活筛选鉴定钙调节热稳定蛋白 1（CARHSP1）作为放射抗性的关键驱动因素。这是一种具有冷休克结构域（CSD）的蛋白质，与冷休克蛋白高度相似。CARHSP1mRNA 水平在辐射抗性 GBM 细胞中上调，CARHSP1 的敲低使 GBM 细胞对放射治疗敏感。CARHSP1 在辐射后的高表达可能通过激活炎症信号通路介导放射抗性。更重要的是，放射治疗后 CARHSP1 水平高的患者生存较差。总之，我们的研究结果表明，靶向放射治疗诱导的 CARHSP1/TNF-α 炎症信号激活可能直接影响放射抗性，并为 GBM 提供了一个有吸引力的治疗靶点，特别是对于 CARHSP1 水平高的患者。
