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The deubiquitinase PSMD14 accelerates cervical cancer progression, with thiolutin offering a novel therapeutic approach
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DOI：10.1186/s13062-026-00930-0.png)
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Abstract
En 中文
Abnormal function of deubiquitination enzymes is implicated in cancer progression. However, the role of the 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in cervical cancer development and its underlying mechanisms remain poorly understood. In our study, we evaluated the role of PSMD14 in the progression of cervical cancer. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to measure differentially expressed PSMD14 in cervical cancer tissues and normal cervical tissues. PSMD14 knockdown and overexpression were performed to investigate the functional role of PSMD14 in vitro and in vivo. The expression and regulation of PSMD14 and PTBP1 were evaluated using immunoprecipitation, western blot analysis. Flow cytometry apoptosis assay was used to detect the cytotoxic effect of THL on cervical cancer cells. PSMD14 is significantly overexpressed in cervical cancer tissues compared to normal cervical tissues. Overexpression of PSMD14 was correlated with myometrial invasion depth and histological classification in cervical cancer patients. Knockdown of PSMD14 in cervical cancer cells led to a significant reduction in proliferation and invasion capabilities in vitro, whereas its overexpression promoted these malignant phenotypes. In a xenograft mouse model, PSMD14 knockdown inhibited tumor growth. Mechanistically, we identified that PSMD14 directly interacts with PTBP1, an RNA-binding protein highly expressed in cervical cancer tissues. Knockdown PSMD14 resulted in decreased PTBP1 protein expression. Notably, we explored the therapeutic potential of THL, a specific inhibitor of PSMD14. THL treatment effectively suppressed cervical cancer cell proliferation, migration, and invasion in vitro, and significantly inhibited tumor growth in vivo without observable toxicity. In summary, our findings reveal an oncogenic role of PSMD14 in cervical cancer progression, highlighting its potential as a diagnostic biomarker and therapeutic target.
Keywords:
Cervical cancer
PSMD14
Thiolutin
Metastasis
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