Nuclear localization of proteasome subunit beta 5 serves as an independent prognostic biomarker and promotes invasion in colorectal cancer

doi:10.4251/wjgo.122057

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Aug 15, 2026; 18(8): 122057
Published online Aug 15, 2026. doi: 10.4251/wjgo.122057

Nuclear localization of proteasome subunit beta 5 serves as an independent prognostic biomarker and promotes invasion in colorectal cancer

Ai-Ping Xu, Shi-Pei She, Yi-Sheng Xiao, Jia Lang, Jing-Fang Yuan, Yuan-Feng Zeng

Ai-Ping Xu, Jia Lang, Jing-Fang Yuan, Yuan-Feng Zeng, Department of Pathology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China

Shi-Pei She, People’s Clinical Medical College, Nanchang University Jiangxi Medical College, Nancang 330006, Jiangxi Province, China

Yi-Sheng Xiao, College of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China

Co-first authors: Ai-Ping Xu and Shi-Pei She.

Author contributions: Xu AP, She SP, Xiao YS, Lang J, and Yuan JF performed the experiments; Xu AP and She SP analyzed the data, and they contributed equally to this manuscript and are co-first authors; Xiao YS contributed to the statistical analysis; Zeng YF conceived and designed the study, drafted the manuscript and revised the manuscript critically for important intellectual content. All authors have read and approved the final manuscript.

AI contribution statement: During the preparation of this manuscript, the AI tool DeepSeek (specifically DeepSeek-V3.1-Terminus) was used solely for language polishing and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated suggestions were critically reviewed and revised by the authors, who assume full responsibility for the accuracy, originality, and integrity of the manuscript.

Supported by National Natural Science Foundation of China, No. 81960432 and No. 82460599; Jiangxi Provincial Natural Science Foundation, No. 20232BAB206091; and Health Commission Science and Technology Program of Jiangxi Province, No. 202410164.

Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Jiangxi Provincial People’s Hospital [Approval No. KeKuai-2024-(15)].

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. The data are not publicly available due to patient privacy and institutional restrictions.

Corresponding author: Yuan-Feng Zeng, PhD, Chief, Chief Physician, Director, Full Professor, Department of Pathology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 152 Aiguo Road, Donghu District, Nanchang 330006, Jiangxi Province, China. zyf760928@163.com

Received: April 9, 2026
Revised: May 16, 2026
Accepted: June 22, 2026
Published online: August 15, 2026
Processing time: 121 Days and 6.5 Hours

Abstract

BACKGROUND

The proteasome subunit beta (PSMB) 5 is a core catalytic subunit of the 20S proteasome. While its overexpression is noted in some cancers, the clinical significance of its subcellular localization in colorectal cancer (CRC) remains unexplored.

AIM

To investigate the subcellular localization of PSMB5, its clinical prognostic value, and functional role in invasion and migration in CRC.

METHODS

Immunohistochemistry, reverse transcription quantitative real-time polymerase chain reaction, western blot, and subcellular fractionation were used to investigate the PSMB5 expression and localization in CRC tissues (n = 129) and cell lines. The prognostic value was assessed using Kaplan-Meier and Cox regression analyses. The PSMB5 functional role was examined using small interfering RNA-mediated knockdown followed by invasion and migration assays.

RESULTS

PSMB5 was significantly overexpressed in tumor tissue clinical samples compared to adjacent normal mucosa. Additionally, it showed heterogeneous subcellular localization (cytoplasmic, nuclear, or both). The high expression and nuclear localization were strongly associated with aggressive clinicopathological features that included poor differentiation, deep invasion, metastasis, and an advanced tumor, node, metastasis stage. Moreover, nuclear PSMB5 localization was identified using a multivariate analysis as an independent prognostic factor for poor overall survival. In vitro, PSMB5 was overexpressed at both the mRNA and protein levels in CRC cell lines; and its nuclear enrichment was markedly heightened in cell lines with metastatic potential. Functionally, the silencing of PSMB5 robustly inhibited the invasive and migratory capacities of CRC cells.

CONCLUSION

Nuclear-localized PSMB5, beyond mere overexpression, may serve as a novel independent prognostic biomarker, a functional requirement for invasion/migration, and a potential therapeutic target in CRC.

Keywords: Colorectal cancer; Proteasome subunit beta 5; Nuclear localization; Prognostic biomarker; Cell migration and invasion; Subcellular fractionation; Small interfering RNA knockdown

Core Tip: This is the first study to investigate the subcellular localization of proteasome subunit beta (PSMB) 5 in colorectal cancer (CRC). We demonstrate that nuclear PSMB5 localization, rather than total PSMB5 expression, serves as an independent prognostic biomarker for poor overall survival in CRC patients. Functional assays show that PSMB5 silencing significantly impairs CRC cell invasion and migration. Notably, metastatic CRC cell lines exhibit higher nuclear-to-cytoplasmic PSMB5 ratios than non-metastatic counterparts. These findings establish nuclear-localized PSMB5 as a novel prognostic indicator and a potential therapeutic target in CRC.