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Published on: October 27, 2014
PSMD7 downregulation suppresses lung cancer progression by regulating the p53 pathway
Xinchun Xu1, Xiaofeng Xuan2, Jieru Zhang2
1Department of Ultrasound, The Affiliated Zhangjiagang Hospital of Soochow University, 68 Jiyang West Road, Suzhou, 215600, China.
Abstract:
Lung cancer is the second most common cancer in both men and women. The deubiquitinase PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of lung cancer remain largely unknown. In this study, we assessed PSMD7 expression and investigated the underlying molecular events by which PSMD7 regulates tumor progression in non-small cell lung cancer (NSCLC). The results showed that PSMD7 is more highly expressed in NSCLC tissues than in adjacent noncancerous tissues. PSMD7 expression was also closely associated with lymph node invasion and the laterality of the tumor in lung adenocarcinoma (LUAD). A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in LUAD patients, and PSMD7 knockdown significantly reduced cell proliferation and induced G0/G1-phase cell cycle arrest, cell senescence and apoptosis. PSMD7 knockdown inhibited expression of a set of proteins regulating cell cycle progression. Depletion of PSMD7 increased p53 levels and induced p21 and puma expression in a p53-dependent manner. Importantly, knockdown of PSMD7 markedly inhibited LUAD tumor growth in a xenograft mouse model. Taken together, these findings indicate that PSMD7 may serve as a valuable prognostic indicator and potential therapeutic target in LUAD.
Insights
The deubiquitinase PSMD7 is highly expressed in non-small cell lung cancer (NSCLC), promoting tumor growth and progression. Inhibiting PSMD7 offers a potential therapeutic strategy for lung adenocarcinoma (LUAD).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung cancer is a leading cause of cancer-related deaths globally.
- The deubiquitinase PSMD7 is a key component of the 26S proteasome, involved in protein degradation.
- The role of PSMD7 in non-small cell lung cancer (NSCLC) progression is not well understood.
Purpose of the Study:
- To investigate the expression and function of PSMD7 in non-small cell lung cancer (NSCLC).
- To determine if PSMD7 can serve as a prognostic biomarker and therapeutic target in lung adenocarcinoma (LUAD).
Main Methods:
- PSMD7 expression analysis in NSCLC tissues and adjacent noncancerous tissues.
- PSMD7 knockdown experiments in LUAD cell lines and xenograft mouse models.
- Cell cycle, apoptosis, and senescence assays.
- Western blot analysis to assess protein expression levels.
Main Results:
- PSMD7 expression is significantly upregulated in NSCLC tissues compared to normal tissues.
- High PSMD7 expression correlates with lymph node metastasis and poorer overall survival (OS) and disease-free survival (DFS) in LUAD patients.
- PSMD7 knockdown inhibits LUAD cell proliferation, induces cell cycle arrest, senescence, and apoptosis.
- PSMD7 depletion increases p53 levels and downstream targets (p21, PUMA) in a p53-dependent manner.
- PSMD7 knockdown significantly suppresses LUAD tumor growth in vivo.
Conclusions:
- PSMD7 is oncogenic in NSCLC, promoting tumor progression and inhibiting apoptosis.
- PSMD7 is a potential prognostic biomarker for LUAD.
- Targeting PSMD7 represents a promising therapeutic strategy for LUAD.
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