ArticlePeerJ2017
NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1.
Article in PeerJ, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Heterogeneous and novel transcript expression in single cells of patient-derived clear cell renal cell carcinoma organoids.Genome research · 2025Article
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
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- Article
- An m6A-Driven Prognostic Marker Panel for Renal Cell Carcinoma Based on the First Transcriptome-Wide m6A-seq.Diagnostics (Basel, Switzerland) · 2023Article
- Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker-driven learning framework.Science advances · 2022Article
- Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers.iScience · 2022Article
- Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- c-KIT-ERK1/2 signaling activated ELK1 and upregulated carcinoembryonic antigen expression to promote colorectal cancer progression.Cancer science · 2021Article
- The Role of Artificial Intelligence in the Diagnosis and Prognosis of Renal Cell Tumors.Diagnostics (Basel, Switzerland) · 2021Review
- NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension.Journal of cellular and molecular medicine · 2021Article
- Single-Cell RNA-seq Identification of the Cellular Molecular Characteristics of Sporadic Bilateral Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Article
- Single-Cell RNA Sequencing in Multiple Pathologic Types of Renal Cell Carcinoma Revealed Novel Potential Tumor-Specific Markers.Frontiers in oncology · 2021Article
- Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer.Biological research · 2020Article
- Macrophage HIF-1α Is an Independent Prognostic Indicator in Kidney Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial-Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production.Frontiers in cell and developmental biology · 2020Article
- Article
- Efficient proximal gradient algorithm for inference of differential gene networks.BMC bioinformatics · 2019Article
- Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress.Thoracic cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClear 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.
methodsThe 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.
resultsNDUFA4L2 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.
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