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Updated: Feb 18, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1
Lei Wang1, Zhiqiang Peng2, Kaizhen Wang2
1Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background:
Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated.
Methods:
The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were mined to verify the change of NDUFA4L2 expression level in ccRCC tissues. The correlation between expression level of NDUFA4L2 and cell proliferation/apoptosis was explored by Gene Set Enrichment Analysis (GSEA). Protein-protein interaction (PPI) network of NDUFA4L2 was constructed. Biological process and involved pathways of NDUFA4L2 were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription factors (TFs) which can induce the expression of NDUFA4L2 were explored in clinical samples by correlation analysis and its regulation on the expression of NDUFA4L2 was verified by knockdown experiment.
Results:
NDUFA4L2 was verified to be overexpressed in ccRCC tissues and its expression level was increased accordingly as the American Joint Committee on Cancer (AJCC) stage progressed. A high NDUFA4L2 level predicted the poor prognosis of ccRCC patients and correlated with enhanced cell proliferation and anti-apoptosis. NDUFA4L2 may interact with 14 tumor-related proteins, participate in growth and death processes and be involved in ccRCC-related pathways, such as insulin-like growth factor 1 (IGF-1), mammalian target of Rapamycin (mTOR) and phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT). ETS domain-containing protein ELK1 level positively correlated with the level of NDUFA4L2 in ccRCC tissues and ELK1 could regulate the expression of NDUFA4L2 in ccRCC cells.
Discussion:
NDUFA4L2 upregulation was associated with ccRCC malignancy. NDUFA4L2 expression was regulated by ELK1 in ccRCC cells. Our study provided potential mechanisms by which NDUFA4L2 affected ccRCC occurrence and progression.
Insights
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) is upregulated in clear cell renal cell carcinoma (ccRCC), correlating with malignancy and poor prognosis. The transcription factor ELK1 regulates NDUFA4L2 expression in ccRCC cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a lethal kidney cancer with poorly understood pathogenesis.
- NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) is implicated in ccRCC development.
- Investigating NDUFA4L2's role and regulation is crucial for therapeutic advancements.
Purpose of the Study:
- To elucidate the mechanisms underlying NDUFA4L2's function and upregulation in ccRCC.
- To determine the correlation between NDUFA4L2 expression and ccRCC progression.
- To identify regulatory factors of NDUFA4L2 in ccRCC.
Main Methods:
- Analysis of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets.
- Gene Set Enrichment Analysis (GSEA) for cell proliferation and apoptosis.
- Construction of protein-protein interaction (PPI) networks.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Correlation analysis and knockdown experiments to identify transcription factors.
Main Results:
- NDUFA4L2 is overexpressed in ccRCC tissues, with levels increasing with AJCC stage.
- High NDUFA4L2 expression predicts poor prognosis, enhanced proliferation, and anti-apoptosis.
- NDUFA4L2 interacts with tumor proteins and is involved in IGF-1, mTOR, and PI3K/AKT pathways.
- ETS domain-containing protein ELK1 positively correlates with NDUFA4L2 and regulates its expression.
Conclusions:
- NDUFA4L2 upregulation is linked to ccRCC malignancy and progression.
- ELK1 is identified as a regulator of NDUFA4L2 expression in ccRCC.
- This study offers insights into NDUFA4L2's role in ccRCC pathogenesis.
