An Analysis Regarding the Association Between Proteasome (PSM) and Hepatocellular Carcinoma (HCC)

Abstract

Wei Huang,1,2,* Jia Mei,3,* Yuan-Jie Liu,1,4 Jie-Pin Li,1,4,5 Xi Zou,1,6 Xiao-Ping Qian,2,7 Yu Zhang8 1Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Comprehensive 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; 3Department of Pathology, Nanjing Jinling Hospital, Nanjing, Jiangsu, 210001, People’s Republic of China; 4No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 5Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 6Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, 210023, People’s Republic of China; 7The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China; 8Department of Oncology, Nanjing Jinling Hospital, Nanjing, Jiangsu, 210001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Zhang; Xiao-ping Qian, Email [email protected]; [email protected]: 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.Methods: 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.Results: 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 TP53 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.Conclusion: PSM is a valid predictor of prognosis and therapeutic response in patients with HCC disease. Furthermore, PSMD13 may be a potential therapeutic target.Keywords: hepatocellular carcinoma, proteasome, PSMD13, cell stemness, proliferation

Keywords

• hepatocellular carcinoma
• proteasome
• psmd13
• cell stemness
• proliferation