Dakai Xiao1,2,3, Shengli Yang4, Liyan Huang1,2,3, Huiming He1,2,3, Hui Pan1,2,3, Jianxing He1,2,3. 1. Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 2. Guangzhou Institute of Respiratory Disease, Guangzhou Medical University, Guangzhou 510000, China. 3. The State Key Laboratory of Respiratory Disease, Guangzhou 510120, China. 4. Department of Thoracic Surgery, The First Hospital of Foshan City, Foshan 528000, China.
Abstract
BACKGROUND: The COP9 signalosome (CSN) is an evolutionarily conserved complex composed of eight subunits (CSN1-CSN8). Among the CSN subunits, CSN5 and its dimerization partner CSN6 are the only two MPN (Mpr1-Pad1-N-terminal) domain-containing subunits. These two subunits play essential roles in a variety of biological processes, such as cell cycle progression, protein stability and signal transduction. However, their expression patterns and clinical significance in lung cancer are not completely clear. METHODS: We examined the expressions of both CSN5 and CSN6 in lung adenocarcinoma (LUAD) patients (n=59) using immunohistochemistry analysis, and correlated their expressions with clinicopathological characteristics. MTT cell proliferation assay was performed to determine the effect of CSN5 silencing or overexpression on the growth of lung cancer cells. Knock down or overexpression of CSN5 was confirmed by western blotting. RESULTS: CSN5 expression was elevated in tumor cells, compared to the stromal compartment and adjacent normal epithelial cells. Interestingly, CSN5 was also expressed in the macrophages and lymphocytes adjacent to the tumors. Surprisingly, CSN6 was barely detected in the tumor cells of LUAD patients. Furthermore, we also demonstrated that higher levels of CSN5 were correlated with high tumor-node-metastasis (TNM) stage and worse clinical outcomes. Multivariate Cox regression analysis revealed CSN5 was an independently prognostic factor for LUAD patients. Additionally, in cellular model, depletion of CSN5 expression significantly suppressed the growth of lung cancer cells. CONCLUSIONS: COP9 signalosome subunit CSN5, but not CSN6, is upregulated in LUAD. Moreover, CSN5 is a critical regulator for the growth of lung cancer and represents an independent prognostic factor and a promising therapeutic target for LUAD patients.
BACKGROUND: The COP9 signalosome (CSN) is an evolutionarily conserved complex composed of eight subunits (CSN1-CSN8). Among the CSN subunits, CSN5 and its dimerization partner CSN6 are the only two MPN (Mpr1-Pad1-N-terminal) domain-containing subunits. These two subunits play essential roles in a variety of biological processes, such as cell cycle progression, protein stability and signal transduction. However, their expression patterns and clinical significance in lung cancer are not completely clear. METHODS: We examined the expressions of both CSN5 and CSN6 in lung adenocarcinoma (LUAD) patients (n=59) using immunohistochemistry analysis, and correlated their expressions with clinicopathological characteristics. MTT cell proliferation assay was performed to determine the effect of CSN5 silencing or overexpression on the growth of lung cancer cells. Knock down or overexpression of CSN5 was confirmed by western blotting. RESULTS: CSN5 expression was elevated in tumor cells, compared to the stromal compartment and adjacent normal epithelial cells. Interestingly, CSN5 was also expressed in the macrophages and lymphocytes adjacent to the tumors. Surprisingly, CSN6 was barely detected in the tumor cells of LUAD patients. Furthermore, we also demonstrated that higher levels of CSN5 were correlated with high tumor-node-metastasis (TNM) stage and worse clinical outcomes. Multivariate Cox regression analysis revealed CSN5 was an independently prognostic factor for LUAD patients. Additionally, in cellular model, depletion of CSN5 expression significantly suppressed the growth of lung cancer cells. CONCLUSIONS: COP9 signalosome subunit CSN5, but not CSN6, is upregulated in LUAD. Moreover, CSN5 is a critical regulator for the growth of lung cancer and represents an independent prognostic factor and a promising therapeutic target for LUAD patients.
Authors: Yaw Asare; Erdenechimeg Shagdarsuren; Johannes A Schmid; Pathricia V Tilstam; Jochen Grommes; Omar El Bounkari; Anke K Schütz; Christian Weber; Menno P J de Winther; Heidi Noels; Jürgen Bernhagen Journal: Thromb Haemost Date: 2013-05-02 Impact factor: 5.249
Authors: Anita Schlierf; Eva Altmann; Jean Quancard; Anne B Jefferson; René Assenberg; Martin Renatus; Matthew Jones; Ulrich Hassiepen; Michael Schaefer; Michael Kiffe; Andreas Weiss; Christian Wiesmann; Richard Sedrani; Jörg Eder; Bruno Martoglio Journal: Nat Commun Date: 2016-10-24 Impact factor: 14.919