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EPHX2 overexpression deters the advancement of clear cell renal cell carcinoma via lipid metabolism reprogramming
Bo Guan1, Cong Huang2,3,4, Jun He2,3,4
1Department of Urology, Fuyang People's Hospital, Fuyang, China.
Background:
Clear cell renal cell carcinoma (ccRCC) is a prevalent and highly aggressive subtype of renal cancer. EPHX2, a metabolic regulator with tumor-suppressive properties, not only influences cell cycle dynamics but also interacts with multiple signaling pathways to inhibit tumor growth. However, the specific mechanistic role of EPHX2 in tumorigenesis remains largely unexplored.
Objective:
To elucidate the mechanistic role of EPHX2 in the progression of ccRCC.
Methods:
Bulk transcriptome data, single-cell transcriptome data, and gene set data for ccRCC were sourced from the TCGA database and GEO database. An integrated machine learning approach was employed, utilizing the TCGA dataset as the training set and the MTAB dataset as the test set, to develop prognostic models. Subsequently, EPHX2 was stably overexpressed in the 786-O and ACHN cell lines via lentiviral transfection technology, and its functional effects were validated through in vitro experiments.
Results:
Through ADIPOGENESIS gene set scoring and differential expression analysis, ten key genes, including EPHX2, were identified. Notably, EPHX2 expression was significantly lower in ccRCC tumor tissues compared to normal renal tissues (P < 0.001). Furthermore, overexpression of EPHX2 significantly inhibited the proliferative, migratory, and invasive capacities of ccRCC cell lines.
Conclusion:
EPHX2 plays a pivotal role in the pathophysiological processes of ccRCC, suggesting its potential as a therapeutic target and prognostic biomarker.
Insights
Epoxide hydrolase 2 (EPHX2) acts as a tumor suppressor in clear cell renal cell carcinoma (ccRCC). Lower EPHX2 expression correlates with ccRCC, and its restoration inhibits cancer cell proliferation and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype.
- Epoxide hydrolase 2 (EPHX2) is a metabolic regulator with known tumor-suppressive functions.
- The precise role of EPHX2 in ccRCC tumorigenesis requires further investigation.
Purpose of the Study:
- To investigate the mechanistic role of EPHX2 in clear cell renal cell carcinoma (ccRCC) progression.
- To evaluate EPHX2 as a potential prognostic biomarker and therapeutic target in ccRCC.
Main Methods:
- Utilized TCGA and GEO databases for ccRCC transcriptome and gene set data.
- Developed prognostic models using a machine learning approach with TCGA and MTAB datasets.
- Overexpressed EPHX2 in ccRCC cell lines (786-O, ACHN) and performed in vitro functional validation.
Main Results:
- Identified EPHX2 as a key gene through ADIPOGENESIS gene set scoring and differential expression analysis.
- Found significantly lower EPHX2 expression in ccRCC tissues compared to normal renal tissues (P < 0.001).
- Demonstrated that EPHX2 overexpression significantly reduced ccRCC cell proliferation, migration, and invasion.
Conclusions:
- EPHX2 is a critical factor in the pathophysiology of ccRCC.
- EPHX2 exhibits potential as both a prognostic biomarker and a therapeutic target for ccRCC.
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