Open Access

ARTICLE

PSMB9 Promotes the Malignant Progression of Colorectal Cancer by Regulating the PI3K/Akt Pathway

Wen Gao^1,2, Xingyu Zheng^1,2, Yanan Hu^1,2, Rui Zou³, Yongan Zhou⁴, Xiang Song^2,*

1 The Second Clinical Medical College of Shanxi Medical University, Taiyuan, China
2 Department of Oncology, the Second Hospital of Shanxi Medical University, Taiyuan, China
3 The Sixth Clinical Medical College of Shanxi Medical University, Taiyuan, China
4 Department of Blood Transfusion, the Second Hospital of Shanxi Medical University, Taiyuan, China

* Corresponding Author: Xiang Song. Email:

(This article belongs to the Special Issue: Identification of potential targets and biomarkers for cancers and the exploration of novel molecular mechanisms of tumorigenesis and metastasis)

Oncology Research 2026, 34(9), 24 https://doi.org/10.32604/or.2026.082652

Received 19 March 2026; Accepted 06 July 2026; Issue published 13 August 2026

Abstract

Background: As a core component of the immunoproteasome, the β1i subunit (proteasome 20S subunit beta 9, PSMB9) is involved in antigen processing and presentation and regulates anti-tumor immune responses. PSMB9 is aberrantly overexpressed in colorectal cancer. However, the precise mechanisms through which PSMB9 contributes to the initiation, progression, and immune regulation of colorectal cancer remain unclear. This study aims to investigate the expression characteristics and biological functions of PSMB9 in colorectal cancer, and to further elucidate the molecular pathways underlying its role in colorectal cancer initiation and progression. The findings are expected to provide a theoretical basis for the development of targeted therapeutic strategies against colorectal cancer. Methods: PSMB9 expression in colorectal cancer was analyzed using the TCGA, GEO, GEPIA, and HPA databases, and further validated in normal colonic epithelial cells and colorectal cancer cell lines by RT-qPCR and Western blot. Lentiviral transduction was used to establish stably transduced HCT116 and SW480 cell lines with PSMB9 knockdown and overexpression, respectively. Cell proliferation, migration, and invasion were assessed by CCK-8, colony formation, wound healing, and Transwell assays. Key proteins of the PI3K/Akt signaling pathway were detected by Western blot. Results: PSMB9 was significantly upregulated at both the mRNA and protein levels in colorectal cancer tissues and cell lines. PSMB9 knockdown significantly inhibited the proliferation, migration, and invasion of colorectal cancer cells, while overexpression enhanced these malignant phenotypes. Mechanistically, PSMB9 exerted oncogenic effects through activation of the PI3K/Akt signaling pathway. Conclusions: PSMB9 promotes the malignant progression of colorectal cancer by regulating the PI3K/Akt signaling pathway.

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