山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (7): 12-16.doi: 10.6040/j.issn.1671-7554.0.2016.1655
宗帅,肖东杰,刘华,郏雁飞,马晓丽,李焕杰,黎娉,郑燕,汪运山
ZONG Shuai, XIAO Dongjie, LIU Hua, JIA Yanfei, MA Xiaoli, LI Huanjie, LI Ping, ZHENG Yan, WANG Yunshan
摘要: 目的 探讨CSN5在胃癌中的表达及与患者预后的关系。 方法 运用cBioportal分析工具,分析CSN5在胃癌中基因水平的改变情况;运用qRT-PCR方法检测CSN5 mRNA在永生化的正常胃黏膜细胞株及不同胃癌细胞株中的表达;运用Oncomine数据库(DErrico、Chen胃癌数据集)和TCGA数据库(375例胃癌组织和32例癌旁组织),分析CSN5 mRNA在胃癌组织与正常胃黏膜表达的差异性;运用生存期分析软件Kaplan-Meier plotter,分析CSN5对876例胃癌患者预后的影响;运用Chen胃癌数据集,分析胃癌患者5年生存状态与CSN5表达的关系。 结果 在胃癌中CSN5主要的基因改变形式为扩增;CSN5 mRNA在多种胃癌细胞株中的表达水平显著高于正常胃黏膜细胞株;CSN5 mRNA在胃癌中的表达显著高于正常胃黏膜。生存分析结果发现,CSN5高表达的患者总生存期较长,CSN5低表达的患者总生存期较短。 结论 CSN5在胃癌组织中高表达,且其表达水平与胃癌患者的预后呈正相关,即CSN5高表达的患者,预后较好。
中图分类号:
| [1] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108. [2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. [3] Elimova E, Wadhwa R, Shiozaki H, et al. Molecular biomarkers in gastric cancer[J]. J Natl Compr Canc Netw, 2015, 13(4): e19-29. [4] Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes[J]. Nat Med, 2015, 21(5): 449-456. [5] Wei N, Deng XW. The COP9: a new genetic locus involved in light- regulated development and gene expression in arabidopsis[J]. Plant Cell, 1992, 4(12): 1507-1518. [6] Zhao R, Yeung SC, Chen J, et al. Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers[J]. J Clin Invest, 2011, 121(3): 851-865. [7] Yang X, Menon S, Lykke-Andersen K, et al. The COP9 signalosome inhibits p27(kip1)degradation and impedes G1- S phase progression via deneddylation of SCF Cul1[J]. Curr Biol, 2002, 12(8): 667-672. [8] Zhang XC, Chen J, Su CH, et al. Roles for CSN5 in control of p53/MDM2 activities[J]. J Cell Biochem, 2008, 103(4): 1219-1230. [9] Xue Y, Chen J, Choi HH, et al. HER2-Akt signaling in regulating COP9 signalsome subunit 6 and p53[J]. Cell Cycle, 2012, 11(22): 4181-4190. [10] Fang L, Lu W, Choi HH, et al. ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development[J]. Cancer Cell, 2015, 28(2): 183-197. [11] Gao S, Fang L, Phan LM, et al. COP9 signalosome subunit 6(CSN6)regulates E6AP/UBE3A in cervical cancer[J].Oncotarget,2015,6(29):28026-28041. doi: 10.18632/oncotarget.4731. [12] Li L, Deng XW. The COP9 signalosome: an alternative lid for the 26S proteasome?[J]. Trends Cell Biol, 2003, 13(10): 507-509. [13] Kouvaraki MA, Rassidakis GZ, Tian L, et al. Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1)[J]. Cancer Res, 2003, 63(11): 2977-2981. [14] Sun L, Dong Y, Ohno M, et al. Jab1 expression is associated with inverse expression of p27(kip1)and poor prognosis in epithelial ovarian tumors[J]. Clin Cancer Res, 2001, 7(12): 4130-4135. [15] Pan Y, Wang S, Su B, et al. Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression[J]. Oncogene, 2017, 36(8): 1069-1079. [16] Tomoda K, Kubota Y, Arata Y, et al. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex[J]. J Biol Chem, 2002, 277(3): 2302-2310. [17] Pan Y, Zhang Q, Tian L, et al. Jab1/CSN5 negatively regulates p27 and plays a role in the pathogenesis of nasopharyngeal carcinoma[J]. Cancer Res, 2012, 72(7): 1890-1900. [18] Sang MM, Du WQ, Zhang RY, et al. Suppression of CSN5 promotes the apoptosis of gastric cancer cells through regulating p53-related apoptotic pathways[J]. Bioorg Med Chem Lett, 2015, 25(15): 2897-2901. [19] Duda DM, Borg LA, Scott DC, et al. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation[J]. Cell, 2008, 134(6): 995-1006. [20] Gusmaroli G, Figueroa P, Serino G, et al. Role of the MPN subunits in COP9 signalosome assembly and activity, and their regulatory interaction with Arabidopsis Cullin3-based E3 ligases[J]. Plant Cell, 2007, 19(2): 564-581. [21] Cope GA, Suh GS, Aravind L, et al. Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1[J]. Science, 2002, 298(5593): 608-611. [22] Dominguez-Sola D, Dalla-Favera R. PINning down the c-Myc oncoprotein[J]. Nat Cell Biol, 2004, 6(4): 288-289. [23] Chen J, Shin JH, Zhao, et al. CSN6 drives carcinogenesis by positively regulating Myc stability[J]. Nat Commun, 2014, 5: 5384. doi: 10.1038/ncomms6384. [24] Karlsson A, Deb-Basu D, Cherry A, et al. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression[J]. Proc Natl Acad Sci U S A, 2003, 100(17): 9974-9979. [25] Felsher DW, Bishop JM. Transient excess of MYC activity can elicit genomic instability and tumorigenesis[J]. Proc Natl Acad Sci U S A, 1999, 96(7): 3940-3944. [26] Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins[J]. Nat Rev Mol Cell Biol, 2005, 6(8): 635-645. [27] Guo H, Jing L, Cheng Y, et al. Down-regulation of the cyclin-dependent kinase inhibitor p57 is mediated by Jab1/Csn5 in hepatocarcinogenesis[J]. Hepatology, 2016, 63(3): 898-913. |
| [1] | 李梓绮,魏闫若雪,刘晓晗,刘春铖,赵然,刘玉昆. 长链非编码RNA HEATR3反义RNA 1参与结直肠癌发生发展的功能及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(9): 108-115. |
| [2] | 刘保国,宋翔,赵晓文,毛亚丽. 血清STAT5B、NKAIN1 mRNA检测在乳腺癌中的应用价值[J]. 山东大学学报 (医学版), 2025, 63(7): 68-74. |
| [3] | 王磊,常霄,王梓萌,李娇娇,崔书君,杨飞,朱月香. 瘤内及瘤周DCE-MRI影像组学对宫颈癌患者无进展生存期的预测价值[J]. 山东大学学报 (医学版), 2025, 63(6): 45-54. |
| [4] | 贾若曦,吕丽,刘涵云,吴寅平,李凤彩,赵泽华,王凯,范玉琛. 血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭患者28天预后的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(6): 89-99. |
| [5] | 杜雪,李春霞,刘云霞,张涛. 基于MFPC-Cox的结直肠癌患者预后动态预测模型[J]. 山东大学学报 (医学版), 2025, 63(5): 101-110. |
| [6] | 杨卫芳,徐宏,刘元涛,赵蕙琛. 促甲状腺激素受体抗体在Graves病复发中的作用机制及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(4): 116-121. |
| [7] | 张洁,赵颖慧,董雅琪,李娟,李培龙,杜鲁涛. GPR133基因甲基化在早期胃癌淋巴结转移预测中的作用[J]. 山东大学学报 (医学版), 2025, 63(3): 76-84. |
| [8] | 刘文钊,张远,马湘萍,魏峰涛,卜培莉. 内皮活化和应激指数预测值与心力衰竭患者死亡风险的关联[J]. 山东大学学报 (医学版), 2025, 63(11): 27-35. |
| [9] | 陈文亮,王欢欢,郝金锦,弓蕊,赵强,张飞,高磊,董静逊. lncRNA PVT1表达在胃癌预后评估及恶性进展中的作用:基于列线图模型与细胞功能实验的研究[J]. 山东大学学报 (医学版), 2025, 63(10): 61-71. |
| [10] | 郭振江,王宁,赵光远,杜立强,崔朝勃,刘防震. 基于机器学习建立术前预测近端胃癌食管切缘阳性模型[J]. 山东大学学报 (医学版), 2024, 62(7): 78-83. |
| [11] | 郭姝画,樊扬,田风,王传新,杜鲁涛,李培龙,郭兴,徐硕. 微原纤维相关蛋白3在调控胶质瘤干细胞间充质表型转化中的作用[J]. 山东大学学报 (医学版), 2024, 62(6): 9-16. |
| [12] | 魏闫若雪,李梓绮,刘春铖,刘晓晗,赵然,刘玉昆. 结直肠癌中SP1的瘤内异质性表达及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(5): 89-94. |
| [13] | 刘春铖,刘晓晗,魏闫若雪,李梓绮,刘玉昆,赵然. 结直肠癌中含溴结构域蛋白9的亚细胞定位模式及其临床意义[J]. 山东大学学报 (医学版), 2024, 62(4): 24-30. |
| [14] | 郭鑫,孟君,郑世良,董秀红. 老年胃癌患者衰弱与人体成分的相关性[J]. 山东大学学报 (医学版), 2024, 62(4): 40-47. |
| [15] | 杨雪彦,吴寅平,吕丽,赵泽华,马行宇,李凤彩,王凯,范玉琛. 单核细胞与淋巴细胞比值动态变化对慢加急性乙型肝炎肝衰竭预后的诊断价值[J]. 山东大学学报 (医学版), 2024, 62(3): 61-69. |
|
||