Huang Wei, Mei Jia, Liu Yuan-Jie, Li Jie-Pin, Zou Xi, Qian Xiao-Ping, Zhang Yu
Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People's Republic of China.
Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, People's Republic of China.
J Hepatocell Carcinoma. 2023 Mar 30;10:497-515. doi: 10.2147/JHC.S404396. eCollection 2023.
The Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited.
This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in vivo and in vitro were performed to explore the function of the 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) in HCC.
HCC patients can be divided into two clusters. Cluster 1 (C1) patients having a significantly worse prognosis than Cluster (C2). Two subtypes had significant differences in proliferation-related signaling. In particular, the frequency of mutation was significantly higher in C1 than in C2. In addition, PSM-associated genes were highly consistent with the expression of DNA repair-related signatures, suggesting a potential link between PSM and genomic instability. We also found that downregulation of PSMD13 expression significantly inhibited stemness of tumor cells and impaired the Epithelial mesenchymal transition (EMT) process. Finally, the correlation between the PSMD13 and Ki67 was found to be strong.
PSM is a valid predictor of prognosis and therapeutic response in patients with HCC disease. Furthermore, PSMD13 may be a potential therapeutic target.
蛋白酶体（PSM）是一种大型多催化蛋白酶复合物，由一个20S核心颗粒和一个19S调节颗粒组成，其主要功能是接受并降解泛素化底物，目前被认为是肿瘤增殖和干性维持的潜在调节因子之一。然而，迄今为止，关于PSM与肝细胞癌（HCC）之间关系的研究有限。
本研究采用生物信息学方法结合验证实验，以探究可能与PSM相关的生物学机制。进行了一系列体内和体外实验，以探讨26S蛋白酶体非ATP酶调节亚基13（PSMD13）在HCC中的功能。
HCC患者可分为两个簇。簇1（C1）患者的预后明显比簇2（C2）差。两个亚型在增殖相关信号传导方面存在显著差异。特别是，C1中的突变频率明显高于C2。此外，PSM相关基因与DNA修复相关特征的表达高度一致，表明PSM与基因组不稳定之间存在潜在联系。我们还发现，PSMD13表达的下调显著抑制肿瘤细胞的干性，并损害上皮-间质转化（EMT）过程。最后，发现PSMD13与Ki67之间的相关性很强。
PSM是HCC疾病患者预后和治疗反应的有效预测指标。此外，PSMD13可能是一个潜在的治疗靶点。
