AUTHOR=Peng Xingyu , Liu Zitao , Luo Chen , Sun Rui , Zhang Yuting , Li Bowen , Zou Yeqing , Zhu Jinfeng , Yuan Rongfa 

TITLE=PSMD12 promotes hepatocellular carcinoma progression by stabilizing CDK1

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1581398

DOI=10.3389/fimmu.2025.1581398

ISSN=1664-3224

ABSTRACT=Proteasome 26S subunit non-ATPase 12 (PSMD12), a critical subunit of the proteasome system, is essential for maintaining protein homeostasis. However, its role in hepatocellular carcinoma (HCC) remains underexplored. Bioinformatics analysis, immunohistochemistry, Western blotting, and qRT-PCR confirmed the upregulation of PSMD12 in HCC tissues compared to normal liver tissues, with this overexpression correlating with poor patient prognosis. Functional assays revealed that PSMD12 knockdown suppressed HCC cell proliferation and migration, inducing G2/M phase cell cycle arrest. In contrast, PSMD12 overexpression promoted these malignant behaviors. Mechanistically, PSMD12 interacts with cyclin-dependent kinase 1 (CDK1), preventing its degradation through deubiquitination, thereby accelerating HCC progression by enhancing cell cycle progression. These findings underscore PSMD12’s role in HCC and highlight its potential as both a prognostic biomarker and therapeutic target, providing new insights into the molecular mechanisms driving HCC progression.