ShRNA-targeted centromere protein A inhibits hepatocellular carcinoma growth.
ShRNA-targeted centromere protein A inhibits hepatocellular carcinoma growth.
复制标题
DOI：
10.1371/journal.pone.0017794
复制
发表时间：
2011-03-15
期刊：
影响因子：
3.7
通讯作者：
Zhu M
中科院分区：
文献类型：
--
作者：
Li Y;Zhu Z;Zhang S;Yu D;Yu H;Liu L;Cao X;Wang L;Gao H;Zhu M
着丝粒蛋白A（CENP-A）在细胞周期调控和遗传稳定性中起重要作用。本研究旨在探讨其在肝细胞癌（HCC）中的表达模式、临床意义及生物学功能。检测20对新鲜肝癌组织和相应非肿瘤肝组织中CENP-A的mRNA和蛋白表达。对80例石蜡包埋的HCC标本进行CENP-A免疫组化染色，分析其表达的临床意义。使用具有高丰度CENP-A的人HCC细胞系HepG 2来研究操纵CENP-A对HCC生长的影响。采用实时定量聚合酶链反应阵列和Western印迹分析鉴定CENP-A调控的细胞周期控制和凋亡相关基因。结果表明，CENP-A在HCC中相对于邻近非肿瘤组织异常过表达。这种过度表达与血清HBsAg阳性状态、组织学分级增加、高Ki-67指数和P53免疫阳性显著相关。在HepG 2细胞中敲低CENP-A可降低细胞增殖，将细胞周期阻滞在G1期，并增加凋亡。还在体内观察到CENP-A沉默的抗增殖作用。相反，CENP-A过表达促进HCC细胞生长并减少凋亡。此外，许多涉及细胞周期调控和凋亡的基因，包括CHK 2，P21 waf 1，P27 Kip 1，SKP 2，细胞周期蛋白G1，MDM 2，Bcl-2和Bax，通过操纵CENP-A被去调控。CENP-A的过表达在HCC中经常观察到。靶向CENP-A可以抑制HCC生长，可能是通过调节参与细胞周期进展和凋亡的大量基因，从而代表了这种恶性肿瘤的潜在治疗策略。
Centromere protein A (CENP-A) plays important roles in cell-cycle regulation and genetic stability. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC). CENP-A expression at the mRNA and protein levels was examined in 20 pairs of fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for CENP-A was performed on 80 paraffin-embedded HCC specimens, and the clinical significance of its expression was analyzed. A human HCC cell line HepG2 with high abundance of CENP-A was used to study the effects of manipulating CENP-A on HCC growth. Quantitative real-time polymerase chain reaction arrays and Western blot analysis were employed to identify the cell-cycle control- and apoptosis-related genes regulated by CENP-A. The results showed that CENP-A was aberrantly overexpressed in HCCs relative to adjacent nontumor tissues. This overexpression was significantly associated with positive serum HBsAg status, increased histological grade, high Ki-67 index and P53 immunopositivity. Knockdown of CENP-A in HepG2 cells reduced cell proliferation, blocked cell cycle at the G1 phase, and increased apoptosis. The antiproliferative effects of CENP-A silencing were also observed in vivo. Conversely, CENP-A overexpression promoted HCC cell growth and reduced apoptosis. Furthermore, many genes implicated in cell-cycle regulation and apoptosis, including CHK2, P21waf1, P27 Kip1, SKP2, cyclin G1, MDM2, Bcl-2, and Bax, were deregulated by manipulating CENP-A. Overexpression of CENP-A is frequently observed in HCC. Targeting CENP-A can inhibit HCC growth, likely through the regulation of a large number genes involved in cell-cycle progression and apoptosis, and thereby represents a potential therapeutic strategy for this malignancy.
登录
查看更多内容
影响因子：
37.3
作者：
Amato A;Schillaci T;Lentini L;Di Leonardo A
通讯作者：
Di Leonardo A
着丝粒蛋白F表达在人鼻咽癌中的预后意义和治疗意义
影响因子：
37.3
作者：
Cao JY;Liu L;Chen SP;Zhang X;Mi YJ;Liu ZG;Li MZ;Zhang H;Qian CN;Shao JY;Fu LW;Xia YF;Zeng MS
通讯作者：
Zeng MS
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
影响因子：
64.5
作者：
Hori, Tetsuya;Amano, Miho;Fukagawa, Tatsuo
通讯作者：
Fukagawa, Tatsuo