Suppression of CSN5 promotes the apoptosis of gastric cancer cells through regulating p53-related apoptotic pathways

被引：22
|
作者：
Sang, Miao-Miao [1 ]
Du, Wen-Qi [1 ]
Zhang, Rui-Yan [1 ]
Zheng, Jun-Nian [1 ,2 ,3 ]
Pei, Dong-Sheng [1 ]
机构：
[1] Xuzhou Med Coll, Jiangsu Key Lab Biol Canc Therapy, Xuzhou 221002, Jiangsu, Peoples R China
[2] Xuzhou Med Coll, Affiliated Hosp, Ctr Clin Oncol, Xuzhou 221002, Peoples R China
[3] Xuzhou Med Coll, Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou 221002, Jiangsu, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 15期
基金：
中国国家自然科学基金;
关键词：
Gastric cancer; CSN5/Jab1; siRNA; Proliferation; Apoptosis; p53; DOMAIN-BINDING PROTEIN-1; KINASE INHIBITOR P27(KIP1); COP9; SIGNALOSOME; HEPATOCELLULAR-CARCINOMA; CYTOPLASMIC LOCALIZATION; INVERSE EXPRESSION; JAB1; EXPRESSION; POOR-PROGNOSIS; ACTIVATION; DEGRADATION;
D O I：
10.1016/j.bmcl.2015.05.057
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
As one of the COP9 signalosome complex, CSN5 (also known as Jab1) has been confirmed overexpression in many human cancers and affected multiple pathways associating with cell proliferation and apoptosis. Correlation of CSN5 overexpression with poor prognosis for cancer provides evidence that it is involved in the tumorigenesis. However, little is known about the functional role and the underlying mechanism of CSN5 in gastric cancer progression. In the current study, the effect of CSN5 siRNA (small-interfering RNA) on the proliferation and apoptosis of human gastric cancer cells (AGS and MKN45) were examined. Our results showed that knockdown of CSN5 could inhibit proliferation and promote apoptosis of gastric cancer cells. Additionally, suppression of CSN5 expression contributed to the increased expression levels of p53 and Bax. In conclusion, CSN5 overexpression is significantly correlated with gastric cancer progression, and CSN5 could be a novel target in gastric cancer therapy. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2897 / 2901
页数：5
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