BACKGROUND: The 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.
RESULTS: Expressions 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.
CONCLUSIONS: The 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.
Digital Object Identifier (DOI)
This work was supported by the NIH (NIEHS) Training grant T32ES007266 and NCI grants CA098664, Cancer Center Supporting Grant P30CA17758, and CTSA UL1TR000117.
All the data discussed in this study are available as in main figures or in the supplemental data.
Wicker, Christina A. and Izumi, Tadahide, "Analysis of RNA Expression of Normal and Cancer Tissues Reveals High Correlation of COP9 Gene Expression with Respiratory Chain Complex Components" (2016). Toxicology and Cancer Biology Faculty Publications. 56.
Additional file 1: Figure S1 – Figure S2.
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Additional file 2: Table S1 – Table S9.
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Additional file 8: Table S15.