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NCKAP1 Inhibits the Progression of Renal Carcinoma via Modulating Immune Responses and the PI3K/AKT/mTOR Signaling
Xin Zhang1, Jianqing Ye2, Lixiang Sun1
1Central Laboratory, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, China.
Abstract:
Nck-associated protein 1 (NCKAP1) is critical for cytoskeletal functions and various cellular activities, and deregulation of NCKAP1 in many cancers significantly influences the outcomes of malignant diseases. However, the functions of NCKAP1 in the progression of renal cancer are yet unknown. To investigate the specific roles of NCKAP1 in the immune regulation and tumor progression of renal cancer, the expression of NCKAP1 and genetic variations were analyzed across cancer types at different pathological stages via UALCAN and cBioPortal. Immune cell infiltration in renal cancer was also assessed by ssGSEA and single-cell gene expression data from the GEO. RNA sequencing of NCKAP1-overexpressing 769P cells further examined the impact of NCKAP1 on kidney cancer. Our pancancer analyses revealed a complex NCKAP1 expression profile across various cancer types, with reduced levels in renal cancer patients linked to patient prognosis. CIBERSORT and single-cell RNA sequencing revealed the expression patterns of NCKAP1 in different cell lineages in renal cancer and a significant correlation between NCKAP1 and immune cell infiltration in the kidney tumor microenvironment. We further verified that NCKAP1 suppressed cancer cell growth and affected tumor development in renal cancer via the PI3K/AKT/mTOR signaling pathway. Our results indicate that NCKAP1 is a potential predictive marker and treatment target for renal cancer.
Insights
Nck-associated protein 1 (NCKAP1) is crucial in kidney cancer. Lower NCKAP1 levels correlate with poor prognosis and impact immune cell infiltration, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Nck-associated protein 1 (NCKAP1) is vital for cellular functions and cancer progression.
- Its role in renal cancer development and immune regulation remains unclear.
Purpose of the Study:
- To investigate NCKAP1's function in renal cancer progression and immune modulation.
- To explore NCKAP1 as a potential biomarker and therapeutic target in kidney cancer.
Main Methods:
- Pancancer analysis of NCKAP1 expression and variations using UALCAN and cBioPortal.
- Assessment of immune cell infiltration via ssGSEA and single-cell RNA sequencing.
- RNA sequencing of NCKAP1-overexpressing cells and pathway analysis (PI3K/AKT/mTOR).
Main Results:
- NCKAP1 expression varies across cancers; reduced levels in renal cancer correlate with poorer patient outcomes.
- NCKAP1 expression patterns identified in distinct renal cancer cell lineages.
- Significant correlation found between NCKAP1 and immune cell infiltration in the kidney tumor microenvironment.
- NCKAP1 suppresses renal cancer cell growth and tumor development via the PI3K/AKT/mTOR pathway.
Conclusions:
- NCKAP1 plays a significant role in renal cancer progression and immune response.
- NCKAP1 acts as a tumor suppressor in kidney cancer.
- NCKAP1 is a promising predictive marker and therapeutic target for renal cancer.
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