Wicker Christina A, Izumi Tadahide
Department of Toxicology and Cancer Biology, University of Kentucky, 1095 V.A. Dr, Lexington, KY, 40536, USA.
BMC Genomics. 2016 Dec 1;17(1):983. doi: 10.1186/s12864-016-3313-y.
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.
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.
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.
由八个亚基组成的COP9信号体，凭借其去泛素化酶活性参与癌症遗传学，可调节致癌蛋白如IkB和TGFβ的细胞浓度。然而，其在正常细胞生理学中的功能仍不清楚。主要聚焦于头颈部正常组织的基因表达数据，利用癌症基因组图谱（TCGA）数据库来识别与COP9基因协同表达的基因群，特别是与具有COP9催化活性的COP5（CSN5）协同表达的基因群。
发现COP9的七个基因（COPS2、COPS3、COPS4、COPS5、COPS6、COPS7A和COPS8）在正常组织中高度协同表达。相比之下，肿瘤组织中COP9基因的协同表达模式降低。通路分析显示，COP5与其他COP9基因的表达与线粒体相关功能通路高度协调，包括编码呼吸链复合物的基因。
结果表明，TCGA中可获得的匹配正常组织的mRNA表达数据在统计学上是可靠的，对于评估基因在正常生理学以及癌症组织中与功能通路的新关联非常有用。本研究揭示了COP9基因表达与线粒体活性相关基因表达之间的显著相关性。
