Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components

Abstract

BackgroundThe COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.ResultsExpressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, COPS7A, and COPS8) were found to be highly synergistic in the normal tissues. In contrast, the tumor tissues decreased the coordinated expression pattern of COP9 genes. Pathway analysis revealed a high coordination of the expression of the COPS5 and the other COP9 genes with mitochondria-related functional pathways, including genes encoding the respiratory chain complex.ConclusionsThe results indicate that mRNA expression data for the matched normal tissues available in TCGA are statistically reliable, and are highly useful to assess novel associations of genes with functional pathways in normal physiology as well as in the cancer tissues. This study revealed the significant correlation between the expressions of the COP9 genes and those related to the mitochondrial activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3313-y) contains supplementary material, which is available to authorized users.

Dramatic dysbalancing of the Wnt pathway in breast cancers

“…Failure to identify potential targets within the Wnt pathway by their expression levels prompted us to perform, instead of the simplistic single-gene expression analysis, a systems-level investigation of the Wnt pathway in healthy and BC tissues employing the correlation network analysis of gene expressions 23 – 27 . To this end, we computed all pairwise correlation coefficients between the expression levels of the genes encoding components of the Wnt pathway, both for BC samples and healthy controls.…”

“…Network-based analysis provides an alternative to the investigation of changes in expression of individual selected genes 23 – 27 . Approaches of this type have demonstrated their potential in the search for novel drug targets and biomarkers, as exemplified by identification of 26S-proteasome genes as predictors of clinical outcomes in breast cancer 28 or of the exploitation of phosphotyrosine signaling circuits in oncogenic transformation 29 .…”

Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large‐scale analysis of 14 published GWAS datasets in the DRIVE study

“…In the present study, COPS2 rs141308737 has no functional clues from mRNA expression levels. However, a study showed that overexpression of COPS2 was linked to chromosome instability . Functional prediction software shows that rs141308737 is located at the ER motif (Supporting Information Fig.…”

“…However, a study showed that overexpression of COPS2 was linked to chromosome instability. 42 Functional prediction software shows that rs141308737 is located at the ER motif (Supporting Information Fig. S4) and can bind to the CJUN protein (Supporting Information Table S7).…”

CSN1 facilitates proliferation and migration of hepatocellular carcinoma cells by upregulating cyclin A2 expression

“…The high mortality rate of liver cancer is mainly associated with tumor invasion, metastasis and tumor recurrence after surgical resection (6,37). In recent years, a number of studies have confirmed that the CSN superfamily is widely involved in the regulation of several important intracellular pathways, including cell proliferation, migration, invasion and signal transduction, and plays an important role in tumor development (13,(38)(39)(40). For example, CSN5 and CSN6 are highly expressed in myeloma, lung, colon, breast cancer, malignant glioma and leukemia clinical tissues (14).…”