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ECHS1 suppresses renal cell carcinoma development through inhibiting mTOR signaling activation
Lei Wang1, Yijun Qi2, Xi Wang2
1Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Abstract:
Although the management of patients with renal cell carcinoma (RCC) has changed drastically in recent years, it is still faced with the evolving challenge. Elucidation of the mechanisms underlying RCC will help the development of therapies, as well as biomarkers for early diagnosis. In this study, ccRCC tissues from patients in different stages were subject to iTRAQ-based proteomics analysis. 130 common differentially expressed proteins (DEPs) in different stages were found and lipid metabolism pathway was obviously dysregulated in all stages. These 130 common DEPs were enriched in four highly connected subnetworks including metabolic pathway, the TCA cycle, oxidative phosphorylation and fatty acid metabolism. ECHS1, a key enzyme in fatty acid metabolism, was further investigated. ECHS1 expression was significantly downregulated in ccRCC tissues and ECHS1 level discriminated ccRCC tissues in general and in stage I from adjacent normal tissues well and with the area under the receiver operating characteristic curve (AUC) of more than 0.7. ECHS1 overexpression suppressed RCC cell proliferation and migration through inhibiting mTOR pathway activation. ECHS1 may be a novel target for ccRCC therapeutic interventions and diagnostic biomarker for ccRCC.
Insights
This study identifies dysregulated lipid metabolism in clear cell renal cell carcinoma (ccRCC). Downregulation of enzyme ECHS1 suppresses tumor growth and migration, suggesting its potential as a diagnostic biomarker and therapeutic target for kidney cancer.
Area of Science:
- Proteomics
- Oncology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) management is evolving, necessitating deeper understanding of its mechanisms for improved therapies and early diagnosis.
- Identifying molecular alterations in clear cell renal cell carcinoma (ccRCC) is crucial for developing targeted treatments and diagnostic tools.
Purpose of the Study:
- To investigate differentially expressed proteins (DEPs) in ccRCC tissues across different stages using proteomics.
- To identify key molecular pathways and potential biomarkers involved in ccRCC progression.
- To evaluate the functional role of ECHS1 in ccRCC cell behavior and its potential as a therapeutic target.
Main Methods:
- iTRAQ-based proteomics analysis of ccRCC tissues from patients in various stages.
- Bioinformatic analysis to identify common DEPs and enriched pathways.
- Western blotting and immunohistochemistry to validate ECHS1 expression.
- In vitro experiments to assess the effect of ECHS1 overexpression on ccRCC cell proliferation and migration.
Main Results:
- 130 common DEPs were identified across different ccRCC stages, with significant dysregulation in lipid metabolism pathways.
- ECHS1, a fatty acid metabolism enzyme, was significantly downregulated in ccRCC tissues.
- ECHS1 expression effectively discriminated ccRCC tissues from normal tissues (AUC > 0.7).
- ECHS1 overexpression inhibited ccRCC cell proliferation and migration by suppressing mTOR pathway activation.
Conclusions:
- Lipid metabolism is a key dysregulated pathway in ccRCC.
- ECHS1 is a promising diagnostic biomarker for ccRCC, particularly in early stages.
- ECHS1 holds potential as a novel therapeutic target for ccRCC interventions.
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