COX6C

Gene Summary

Gene:COX6C; cytochrome c oxidase subunit 6C
Location:8q22.2
Summary:Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIc, which has 77% amino acid sequence identity with mouse subunit VIc. This gene is up-regulated in prostate cancer cells. A pseudogene has been found on chromosomes 16p12. [provided by RefSeq, Jul 2010]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:cytochrome c oxidase subunit 6C
Source:NCBIAccessed: 31 August, 2019

Ontology:

What does this gene/protein do?
Show (6)
Pathways:What pathways are this gene/protein implicaed in?
Show (1)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: COX6C (cancer-related)

Li L, Li Y, Huang Y, et al.
Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4.
Cancer Sci. 2018; 109(12):3714-3725 [PubMed] Free Access to Full Article Related Publications
Long non-coding RNA MIF-AS1 (lncMIF-AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF-AS1-based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT-PCR. Target relationships between lncRNA-micro RNA (miRNA) and miRNA-mRNA were predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF-AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non-cancerous gastric tissues and cells (P < .05). MiR-212-5p was identified as the most important miRNA linker between lncMIF-AS1 and NDUFA4, which was negatively regulated by lncMIF-AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF-AS1/miR-212-5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.

Chang FW, Fan HC, Liu JM, et al.
Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2-Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors.
Int J Mol Sci. 2017; 18(1) [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers.
RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells.
CONCLUSIONS: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance.

Swierniak M, Pfeifer A, Stokowy T, et al.
Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.
Mol Cell Endocrinol. 2016; 433:130-7 [PubMed] Related Publications
The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity.

Hadife N, Nemos C, Frippiat JP, et al.
Interleukin-24 mediates apoptosis in human B-cells through early activation of cell cycle arrest followed by late induction of the mitochondrial apoptosis pathway.
Leuk Lymphoma. 2013; 54(3):587-97 [PubMed] Related Publications
Interleukin (IL)-24 has death-promoting effects on various proliferating cells including B-cells from chronic lymphocytic leukemia (CLL) and germinal center B-cells, but its molecular mechanisms are poorly understood. Using a B-cell differentiation model and mRNA profiling, we found that recombinant (r)IL-24 stimulated genes of the mitochondrial apoptotic pathway (Bax, Bid, Casp8, COX6C, COX7B) after 36 h, whereas the transcription of genes involved in DNA replication and metabolism was inhibited within 6 h. Unexpectedly, insulin-like growth factor 1 (IGF1), a hormone known to promote cell growth, was stimulated by IL-24. Activated B-cells express receptor for IGF1, to which they become sensitized and undergo apoptosis, a mechanism similar in this respect to IL-24-induced cell death. Furthermore, inhibition of the IGF1 pathway reversed the effects of IL-24. IL-24-mediated apoptosis was also antagonized by pifithrin-alpha, an inhibitor of p53 transactivation. Altogether, these results disclose sequential molecular signals generated by IL-24 in activated B-cells.

Sirchia R, Luparello C
Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA-MB231 breast cancer cells.
Biol Chem. 2007; 388(5):457-65 [PubMed] Related Publications
We have previously shown that PTHrP(38-94) amide restrains growth and invasion in vitro, causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231, for which tumorigenesis was also attenuated in vivo. We have also demonstrated that mid-region PTHrP gains access to the nuclear compartment of these cells and displays DNA-binding properties in vitro by recognizing targets in both cellular chromatin and isolated oligonucleotides. Here, we examined whether PTHrP(38-94) amide was able to modulate gene expression of MDA-MB231 cells, employing a combination of conventional, differential display and semi-quantitative multiplex PCR techniques. The results obtained provide first evidence that PTHrP(38-94) amide can affect gene expression in tumor cells, identifying A4-differentiation protein/PLP2 as up-regulated, and HOX7/MSX1, COX6C, FZD6, OXR1 and TMCO4 as down-regulated genes in treated cells, and suggest that the cytotoxic activity of the peptide can be ascribed, at least in part, to such transcriptional reprogramming.

Bo H, Ghazizadeh M, Shimizu H, et al.
Effect of ionizing irradiation on human esophageal cancer cell lines by cDNA microarray gene expression analysis.
J Nippon Med Sch. 2004; 71(3):172-80 [PubMed] Related Publications
To provide new insights into the molecular mechanisms underlying the effect of irradiation on esophageal squamous cell carcinomas (ESCCs), we used a cDNA microarray screening of more than 4,000 genes with known functions to identify genes involved in the early response to ionizing irradiation. Two human ESCC cell lines, one each of well (TE-1) and poorly (TE-2) differentiated phenotypes were screened. Subconfluent cells of each phenotype were treated with single doses of 2.0 Gy or 8.0 Gy irradiations. After a 15 min incubation time-point, the cells were collected and analyzed. Compared with non-irradiated cells, many genes revealed at least 2-fold upregulation or downregulation at both doses in well or poorly differentiated ESCC cells. The common upregulated genes in well and poorly differentiated cell types at both irradiation doses included SCYA5, CYP51, SMARCD2, COX6C, MAPK8, FOS, UBE2M, RPL6, PDGFRL, TRAF2, TNFAIP6, ITGB4, GSTM3, and SP3 and common downregulated genes involved NFIL3, SMARCA2, CAPZA1, MetAP2, CITED2, DAP3, MGAT2, ATRX, CIAO1, and STAT6. Several of these genes were novel and not previously known to be associated with irradiation. Functional annotations of the modulated genes suggested that at the molecular level, irradiation appears to induce a regularizing balance in ESCC cell function. The genes modulated in the early response to irradiation may be useful in our understanding of the molecular basis of radiotherapy and in developing strategies to augment its effect or establish novel less hazardous alternative adjuvant therapies.

Foa C, Mainguené C, Dupré F, et al.
Rearrangement involving chromosomes 1 and 8 in a retroperitoneal lipoma.
Cancer Genet Cytogenet. 2002; 133(2):156-9 [PubMed] Related Publications
Superficial lipomas are very common benign adipose tissue tumors. In contrast, deep-seated lipomas such as retroperitoneal lipomas, are extremely rare and have to be carefully distinguished from well-differentiated liposarcomas for appropriate treatment and follow-up. We report to, our knowledge, the first cytogenetic analysis of a retroperitoneal lipoma occurring in an adult, which showed a complex rearrangement interpreted as t(1;8)(q32;q22-q23) followed by a pericentric inversion of der(8). There was no detectable rearrangement of chromosome 12, and in particular no 12q14-q15 amplification. Because rearrangements of the 8q11-q13 region involving the PLAG1 gene have been described in lipoblastoma-another kind of benign adipose tumor--we used fluorescence in situ hybridization analysis to determine in the present case the chromosomal breakpoint on 8q was located between the ETO (8q22) and COX6C (8q22-q23) genes at a great distance from PLAG1. Karyotypic analysis of additional cases of retroperitoneal lipomas will be required to assess the significance of chromosome 1 and 8 rearrangements in a continuous effort to attain a better classification of adipose tissue tumors. Of great importance is the determination of such genetic markers as additional tools for the differential diagnosis between benign and malignant forms of adipose tumors, and to avoid erroneous diagnoses.

Mine N, Kurose K, Nagai H, et al.
Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas.
J Hum Genet. 2001; 46(7):408-12 [PubMed] Related Publications
HMGIC, a high-mobility-group protein gene encoding an architectural transcription factor, was recently identified as the target of gene fusion in a variety of human benign mesenchymal tumors; some of these events were chromosomal translocations involving 12q13-15. HMGIC consists of three DNA-binding domains (encoded by exons 1-3), a spacer, and an acidic carboxyl-terminal regulatory domain (exons 4-5). To determine the spectrum and nature of the aberrations in uterine myomas in Japanese patients, we systematically examined the tumors of 45 patients for all possible types of gene fusions involving HMGIC, by means of 3'-rapid amplification of cDNA ends (RACE) and reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. HMGIC gene fusions were found in 16 (36%) of the tumors; aberrant splicings to five cryptic sequences located in introns of the HMGIC gene were found in 11 of these cases, and translocations causing juxtaposition to other genes, such as COX6C and RA D51B, were found in 5. In all fusion transcripts, the first two or three exons of HMGIC were fused to ectopic sequences. Our results suggest that a fusion event, resulting in the separation of the DNA-binding domains of HMGIC from the spacer and the acidic carboxyl-terminal regulatory domain, is a common tumorigenic mechanism in the development of uterine myomas.

Kurose K, Mine N, Doi D, et al.
Novel gene fusion of COX6C at 8q22-23 to HMGIC at 12q15 in a uterine leiomyoma.
Genes Chromosomes Cancer. 2000; 27(3):303-7 [PubMed] Related Publications
Cytogenetic analyses have shown that aberrations involving 12q13-15 are frequent chromosomal changes in a variety of human benign mesenchymal tumors, e.g., pleomorphic adenomas of the parotid gland, pulmonary chondroid hamartomas, lipomas, and uterine leiomyomas. Recently, the high-mobility group protein gene HMGIC was identified as the target gene affected by the 12q13-15 aberrations. Using 3' rapid amplification of cDNA ends experiments, we isolated novel ectopic sequences fused to HMGIC in a uterine leiomyoma. Cloning of the fusion cDNA identified the human cytochrome c oxidase subunit VIc (COX6C) gene on 8q22-23 as the fusion partner of HMGIC. Nucleotide sequences of the fusion transcript revealed that the first 3 exons of the HMGIC gene, encoding the 3 DNA binding domains, was fused to the exon 2 of the COX6C gene. The identification of a gene rearrangement suggests a role for HMGIC in tumorigenesis of uterine leiomyoma and suggests a possible involvement of HMGIC in mesenchymal differentiation. Genes Chromosomes Cancer 27:303-307, 2000.

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Cite this page: Cotterill SJ. COX6C, Cancer Genetics Web: http://www.cancer-genetics.org/COX6C.htm Accessed:

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