文章：

HJURP敲低破坏克隆生成能力，增加辐射诱导的胶质母细胞瘤细胞死亡

HJURP knockdown disrupts clonogenic capacity and increases radiation-induced cell death of glioblastoma cells 

原文发布日期：2019-05-29 

英文摘要：

The Holliday Junction-Recognition Protein (HJURP) was reported as overexpressed in several cancers and also strongly correlated with poor prognosis of patients, especially in glioblastoma (GBM), the most common and deadly type of primary brain tumor. HJURP is responsible for loading the histone H3 variant—the Centromeric Protein A (CENP-A)—at the centromeres in a cell cycle-regulated manner, being required for proper chromosome segregation. Here we investigated HJURP association with survival and radioresistance of different GBM cell lines. HJURP knockdown compromised the clonogenic capacity and severely impaired survival of five distinct GBM cells, while nontumor astrocytes were not affected. U251MG cells showed a robust cell cycle arrest in G2/M phases followed by a drastic increment in cell death after HJURP silencing, while U138MG and U343MG cell lines presented augmented senescence with a comparable increase in cell death. Importantly, we verified that the impact on cell cycle dynamics and clonogenic survival were associated with loss CENP-A at the centromeres. Moreover, radiation resistance was also impacted by HJURP modulation in several GBM cell lines. U87MG, T98G, U138MG, and U343MG cells were all sensitized to ionizing radiation after HJURP reduction. These data reinforce the requirement of HJURP for proliferative capacity and radioresistance of tumor cells, underlining its potential as a promising therapeutic target for GBM. 

摘要翻译： 

据报道，Holliday交叉识别蛋白（HJURP）在多种癌症中过度表达，且与患者不良预后密切相关，尤其在最具侵袭性的原发性脑肿瘤——胶质母细胞瘤（GBM）中表现显著。HJURP负责以细胞周期调控的方式将组蛋白H3变体——着丝粒蛋白A（CENP-A）加载到着丝粒上，这一过程对染色体正常分离至关重要。本研究探讨了HJURP在不同GBM细胞系中与生存能力和放射抗性的关联。敲低HJURP会显著削弱五种不同GBM细胞的克隆形成能力并严重损害其生存，而非肿瘤性星形胶质细胞未受影响。U251MG细胞在HJURP沉默后出现明显的G2/M期细胞周期阻滞，随后细胞死亡急剧增加；而U138MG和U343MG细胞系则呈现衰老增强伴随细胞死亡同步上升。重要的是，我们证实细胞周期动力学和克隆存活能力的变化与着丝粒处CENP-A的缺失相关。此外，多个GBM细胞系的放射抗性也受HJURP调控影响。U87MG、T98G、U138MG和U343MG细胞在HJURP表达降低后对电离辐射的敏感性均增强。这些数据进一步证明HJURP对肿瘤细胞增殖能力和放射抗性具有关键作用，提示其可作为GBM治疗的潜在靶点。

原文链接：

HJURP knockdown disrupts clonogenic capacity and increases radiation-induced cell death of glioblastoma cells