ArticleOncotarget2015
Nuclear-encoded cytochrome c oxidase subunit 4 regulates BMI1 expression and determines proliferative capacity of high-grade gliomas.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Cytochrome c Oxidase Subunit COX4-1 Reprograms Erastin-Induced Cell Death from Ferroptosis to Apoptosis: A Transmitochondrial Study.Antioxidants (Basel, Switzerland) · 2025Article
- Osteogenesis Imperfecta: A Look into the Cerebellum of the Brtl Murine Model.Molecular neurobiology · 2025Article
- Early metabolic reprogramming and carbonic anhydrase IX-mediated extracellular acidification drive radiotherapy-induced glioblastoma cell dedifferentiation.Acta neuropathologica communications · 2025Article
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.Nature communications · 2025Article
- COX-2 Inhibition in Glioblastoma Cells Counteracts Resistance to Temozolomide by Inducing Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Biochanin a modulates steroidogenesis and cellular metabolism in human granulosa cells through TAS2Rs activation: a spotlight on ovarian function.Reproductive biology and endocrinology : RB&E · 2025Article
- Copper-Induced Enhancement of Glioblastoma Tumorigenicity via Cytochrome C Oxidase.Antioxidants (Basel, Switzerland) · 2025Article
- Insights Into the Role of Bmi-1 Deregulation in Promoting Stemness and Therapy Resistance in Glioblastoma: A Narrative Review.Cancer medicine · 2025Review
- The Nuclear-Encoded Cytochrome c Oxidase Subunit COX4-1 Enhances Hypoxia Tolerance in Glioblastoma Cells.Journal of oncology research and therapy · 2025Article
- A Phyto-mycotherapeutic Supplement, NamelyInternational journal of molecular sciences · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Effects of Ferrocene and Ferrocenium on MCF-7 Breast Cancer Cells and Interconnection with Regulated Cell Death Pathways.Molecules (Basel, Switzerland) · 2023Article
- Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2023Article
- Hydroquinidine displays a significant anticarcinogenic activity in breast and ovarian cancer cells via inhibiting cell-cycle and stimulating apoptosis.Turkish journal of biology = Turk biyoloji dergisi · 2023Article
- Label-Free Quantitative Proteomics Analysis of Adriamycin Selected Multidrug Resistant Human Lung Cancer Cells.Biomolecules · 2022Article
- Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells.Metabolites · 2022Article
- COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM.Cell stress · 2022Article
- Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear-encoded cytochrome c oxidase subunit 4 (COX4) is a key regulatory subunit of mammalian cytochrome c oxidase, and recent studies have demonstrated that COX4 isoform 1 (COX4-1) could have a role in glioma chemoresistance. The Polycomb complex protein BMI1 is a stem cell regulatory gene implicated in the pathogenesis of many aggressive cancers, including glioma. This study sought to determine if COX4 regulates BMI1 and modulates tumor cell proliferation. Using The Cancer Genome Atlas database and a retrospective data set from patients with glioblastoma multiforme, we found that BMI1 expression levels positively correlated with COX4-1 expression and overall survival. Whereas COX4-1 promoted cell growth by increasing BMI1 expression, COX4-2 inhibited cell growth even in cells overexpressing BMI1. We also demonstrate that COX4-1 attenuates mitochondrial reactive oxygen species (ROS) production, which is required for COX4-1-mediated effects on BMI1 expression and cell proliferation. Notably, mice bearing COX4-1-expressing glioma cell xenografts quickly developed invasive tumors characterized by the presence of multiple lesions positive for Ki-67, BMI1, and COX4-1, whereas mice bearing COX4-2-expressing xenografts rarely developed tumors by this point. COX4-1 also promoted the self-renewal of glioma stem-like cells, consistent with the reported role of BMI1 in stem cell growth. Taken together, these findings identify a novel COX4-1-mitochondrial ROS axis, in which differential expression of COX4 isoforms regulates mitochondrial ROS production and controls BMI1 expression.
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