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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Overexpression pattern, function, and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma
Sheng-Sheng Zhou, Yu-Ping Ye, Yi Chen, Da-Tong Zeng, Guang-Cai Zheng, Rong-Quan He, Bang-Teng Chi, Lei Wang, Qian Lin, Qin-Yan Su, Yi-Wu Dang, Gang Chen, Jia-Liang Wei
Sheng-Sheng Zhou, Rong-Quan He, Jia-Liang Wei, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Yu-Ping Ye, Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Yi Chen, Bang-Teng Chi, Lei Wang, Qian Lin, Qin-Yan Su, Yi-Wu Dang, Gang Chen, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Da-Tong Zeng, Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Guang-Cai Zheng, Department of Surgery, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Co-first authors: Sheng-Sheng Zhou and Yu-Ping Ye.
Co-corresponding authors: Gang Chen and Jia-Liang Wei.
Author contributions: Zhou SS, Ye YP, Dang YW, He RQ, Chen G and Wei JL contributed to designing topics, guiding statistical analysis, and revising the paper; Zeng DT and Zheng GC provided tissue samples, as well as collected and interpreted clinical data; Chen Y and Chi BT performed the immunohistochemistry; Wang L extracted data from the Cancer Genome Atlas, Gene Expression Omnibus, Sequence Read Archive, ArrayExpress, International Cancer Genome Consortium, DepMap and GDSC databases; Lin Q and Su QY analyzed the data statistically and contributed to the interpretation of the data. Chen Y contributed to drafting the paper; all authors have commented on previous manuscript editions; all authors approved the final version of the article. Zhou SS and Ye YP designed the study, revised the paper, and contributed equally to this study, sharing joint first authorship. Wei JL and Chen G both provided detailed guidance for this paper and are therefore co-corresponding authors.
Supported by National Natural Science Foundation of China, No. 82160762; Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project, No. GXZYA20230267; China Undergraduate Innovation and Entrepreneurship Training Program, No. S202410598060X; China Undergraduate Innovation and Entrepreneurship Training Program, No. X202410598360; Future Academic Star of Guangxi Medical University, No. WLXSZX24074.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of First Affiliated Hospital of Guangxi Medical University and the Ethics Committee of Yulin Redcross Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Gang Chen, PhD, Chief Doctor, Professor, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nan
ning 530021, Guangxi Zhuang Autonomous Region, China.
chengang@gxmu.edu.cn
Received: July 31, 2024
Revised: October 10, 2024
Accepted: November 13, 2024
Published online: February 24, 2025
Processing time: 132 Days and 19.1 Hours
BACKGROUND
In recent years, many studies have shown that proteasome 26S subunit non-ATPase 6 (PSMD6) plays an important role in the occurrence and development of malignant tumours. Unfortunately, there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma (HCC).
AIM
To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.
METHODS
This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues, along with immunohistochemical scores from 383 HCC and adjacent tissues, to assess PSMD6 overexpression in HCC. Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth. Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC. Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.
RESULTS
The results of 41 external and two internal datasets showed that PSMD6 mRNA (SMD = 0.26, 95%CI: 0.09-0.42, P < 0.05) and protein (SMD = 2.85, 95%CI: 1.19-4.50, P < 0.05) were significantly overexpressed in HCC tissues. The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues (SMD = 0.40, 95%CI: 0.15-0.66, P < 0.05). PSMD6 knockout inhibited HCC cell growth (chronos scores < -1). Functional enrichment implicated ribosome biogenesis and RNA splicing. Significant enrichment of signalling pathways such as RNA degradation, ribosomes, and chemical carcinogenesis—reactive oxygen species. Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323, sepantronium bromide, and GDC0810. Overexpressed PSMD6 effectively distinguished HCC tissues (AUC = 0.75, 95%CI: 0.71-0.79).
CONCLUSION
This study was the first to discover that PSMD6 was overexpressed in HCC tissues. PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
Core Tip: This study integrated 8339 hepatocellular carcinoma (HCC) tissue mRNA expression profiles from 41 platforms, 383 pairs of hepatocellular tissue samples from inhouse immunohistochemistry experiments, and HCC cell lines using the clustered regularly interspaced short palindromic repeats system for proteasome 26s subunit non-ATPase 6 (PSMD6) knockout data to evaluate the abnormal expression pattern and clinical significance of PSMD6 in HCC tissues. This study was the first to discover that PSMD6 was overexpressed in HCC tissues. The promotion of PSMD6 in HCC progression is closely related to ribosome biogenesis and RNA splicing, suggesting that PSMD6 may enhance the proliferation of HCC cells.
