文章：

SPRTN通过内质网应激反应参与肝细胞癌的发生发展

SPRTN is involved in hepatocellular carcinoma development through the ER stress response 

原文发布日期：2023-12-12 

英文摘要：

Endoplasmic reticulum (ER) stress, prompted by the accumulation of misfolded or unfolded proteins, triggers the activation of the unfolded protein response (UPR) pathway to restore ER homeostasis. This stress response is implicated in the development of hepatocellular carcinoma (HCC). A biallelic mutation in SPRTN is currently the only known single-gene mutation implicated in the early onset of HCC. However, the exact mechanism linking SPRTN mutations to HCC remains unclear. In our study, we analyzed SPRTN and UPR in 21 human HCC tissue samples using RT-qPCR, immunoblot, and immunohistochemistry. We found alterations in the expression levels of SPRTN and UPR-related genes and proteins in HCC samples. The impact of SPRTN on the ER stress response was assessed in SPRTN-depleted HepG2 cells through RNA sequencing, pull-down assay, comet assay, and mitotic index calculation. We demonstrated that SPRTN interacts with the UPR sensor GRP78. Furthermore, we observed a decrease in SPRTN levels during ER stress, and increased sensitivity to ER stress in SPRTN-depleted cells. These findings suggest an essential role for SPRTN in the ER stress response and provide new insights into HCC pathogenesis. This newly discovered function of SPRTN could significantly enhance our understanding and treatment of HCC. 

摘要翻译：

内质网应激由未折叠或错误折叠蛋白质的积累引发，可激活未折叠蛋白反应通路以恢复内质网稳态。该应激反应与肝细胞癌的发生发展密切相关。目前SPRTN基因的双等位突变是唯一已知与早发性肝细胞癌相关的单基因突变，但其具体致病机制尚不明确。本研究通过RT-qPCR、免疫印迹和免疫组化技术对21例人肝细胞癌组织样本进行分析，发现SPRTN及未折叠蛋白反应相关基因和蛋白表达水平存在异常。通过RNA测序、Pull-down实验、彗星实验及有丝分裂指数计算，我们在SPRTN缺失的HepG2细胞中评估了该基因对内质网应激反应的影响。研究证实SPRTN与内质网应激感应蛋白GRP78存在相互作用，并发现内质网应激状态下SPRTN水平降低，且SPRTN缺失细胞对内质网应激敏感性增强。这些发现揭示了SPRTN在内质网应激应答中的关键作用，为肝细胞癌发病机制提供了新见解。SPRTN新功能的发现有望显著提升我们对肝细胞癌的认知和治疗水平。

原文链接：

SPRTN is involved in hepatocellular carcinoma development through the ER stress response