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NEDD4L suppresses PD-L1 expression and enhances anti-tumor immune response in A549 cells
Bin Zhong1, Jie Zheng2, Huilan Wen1
1Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, No.23, Qingnian Road, Zhanggong District, Ganzhou City, 341000, Jiangxi Province, China.
Background:
Non-small cell lung cancer (NSCLC) poses a salient threat to public health. E3 ubiquitin ligase commonly functions as an anti-tumor role.
Objective:
This study probed the effect of E3 ligase NEDD4L on A549 cells.
Methods:
NEDD4L expression in NSCLC and its correlation with NSCLC patient's prognosis were predicted and verified. PD-L1 protein level was measured, and the correlation between NEDD4L and PD-L1 was analyzed. The effects of NEDD4L overexpression on the binding of NEDD4L to PD-L1 and ubiquitination level of PD-L1 were examined. Xenograft tumor model was established in mice. The volume and weight of xenograft tumors were recorded. The proportion of CD8+ T cells and contents of IL-2 and INF-γ were detected.
Results:
NEDD4L expression was downregulated in NSCLC tissues and A549 cells, and correlated with poor prognosis of NSCLC patients. PD-L1 was upregulated in NSCLC and negatively correlated with NEDD4L. Overexpression of NEDD4L upregulated ubiquitination level of PD-L1 and reduced protein level of PD-L1. Overexpression of NEDD4L decreased tumor volume and weight and enhanced proportion of CD8+ T cells and contents of IL-2 and INF-γ.
Conclusions:
Collectively, overexpression of NEDD4L suppressed PD-L1 protein level through ubiquitination, thereby enhancing anti-tumor immune response and retarding NSCLC progression.
Insights
Overexpression of E3 ligase NEDD4L in non-small cell lung cancer (NSCLC) reduces PD-L1 levels, enhancing anti-tumor immunity and slowing cancer progression. This finding offers a potential therapeutic strategy for NSCLC.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) is a major public health concern.
- E3 ubiquitin ligases play a crucial role in anti-tumor functions.
- The specific role of NEDD4L in NSCLC requires further investigation.
Purpose of the Study:
- To investigate the effect of E3 ligase NEDD4L on NSCLC, specifically in A549 cells.
- To determine the correlation between NEDD4L expression and NSCLC patient prognosis.
- To explore the relationship between NEDD4L and PD-L1 in NSCLC.
Main Methods:
- NEDD4L expression in NSCLC tissues and cells was analyzed.
- Correlation between NEDD4L and PD-L1 protein levels was assessed.
- Effects of NEDD4L overexpression on PD-L1 ubiquitination and tumor growth in a xenograft model were examined.
Main Results:
- NEDD4L was downregulated in NSCLC tissues and cells, correlating with poor prognosis.
- PD-L1 was upregulated in NSCLC and inversely correlated with NEDD4L expression.
- NEDD4L overexpression reduced PD-L1 levels, decreased tumor volume/weight, and enhanced anti-tumor T cell responses.
Conclusions:
- NEDD4L overexpression suppresses PD-L1 protein levels via ubiquitination.
- This mechanism enhances anti-tumor immune response and retards NSCLC progression.
- NEDD4L represents a potential therapeutic target for NSCLC treatment.
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