High expression of CREPT promotes tumor growth and is correlated with poor prognosis in colorectal cancer
High expression of CREPT promotes tumor growth and is correlated with poor prognosis in colorectal cancer
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CREPT 的高表达会促进肿瘤生长，并与结直肠癌的不良预后相关。
DOI：
10.1016/j.bbrc.2016.10.067
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发表时间：
2016-11-18
影响因子：
3.1
通讯作者：
Yang, An-Gang
中科院分区：
文献类型：
--
作者：
Zheng, Guoxu;Li, Weimiao;Yang, An-Gang
CREPT（肿瘤中与细胞周期相关且表达上调的蛋白）在多种癌症中高表达，且已证实对某些癌症具有预后判断价值。然而，CREPT在结直肠癌（CRC）中的临床意义尚未得到充分研究。在本研究中，我们检测了225例临床结直肠癌组织及配对的癌旁正常组织中CREPT的表达情况，并分析了CREPT表达与其他临床病理特征之间的相关性。我们还利用敲低或过表达CREPT的结直肠癌细胞，在体外和体内评估了CREPT的生物学功能。结果显示，225例结直肠癌患者中有175例（77.8%）表达CREPT，且CREPT表达与肿瘤分化程度（P = 0.000）、Dukes分期（P = 0.013）及转移情况（P = 0.038）显著相关。CREPT高表达的患者生存时间往往较短。多因素分析表明，CREPT阳性表达可作为结直肠癌预后的独立预测指标。敲低CREPT的细胞表现出增殖受抑制及细胞周期阻滞，而过表达CREPT的细胞则增殖加快且细胞周期进程加速。此外，CREPT过表达在体内显著促进了肿瘤生长。机制研究显示，CREPT可能通过对细胞周期蛋白D3、细胞周期蛋白依赖性激酶4（CDK4）及细胞周期蛋白依赖性激酶6（CDK6）的调控来调节细胞增殖和细胞周期。（C）2016爱思唯尔公司版权所有。
CREPT (cell cycle-related and expression elevated protein in tumor) is highly expressed in many kinds of cancer, and has been shown to be prognostic in certain cancers. However, the clinical significance of CREPT in colorectal cancer (CRC) has not been sufficiently investigated. In this study, we examined the CREPT expression in 225 clinical CRC tissues and paired adjacent normal tissues, and analyzed the correlation between CREPT expression and other clinicopathological features. We also evaluated the biological function of CREPT both in vitro and in vivo using knockdown or overexpressing CRC cells. Our results showed that CREPT expressed in 175 of 225 (77.8%) CRC patients and the CREPT expression was significantly associated with tumor differentiation (P = 0.000), Dukes' stages (P = 0.013) and metastasis (P = 0.038). Patients with high CREPT expression tended to have shorter survival time. Multivariate analysis showed that positive CREPT expression can be used as an independent predictor for CRC prognosis. CREPT knockdown cells showed inhibited cell proliferation and arrested cell cycle, while CREPT overexpressing cells showed increased proliferation and promoted cell cycle. In addition, CREPT overexpression significantly promoted tumor growth in vivo. Mechanism study showed that CREPT may regulate cell proliferation and cell cycle through the regulation on cyclin D3, CDK4 and CDK6. (C) 2016 Elsevier Inc. All rights reserved.