The orphan nuclear receptor EAR2 is overexpressed in colorectal cancer and it regulates survivability of colon cancer cells
The orphan nuclear receptor EAR2 is overexpressed in colorectal cancer and it regulates survivability of colon cancer cells
复制标题
孤儿核受体 EAR2 在结直肠癌中过度表达，它调节结肠癌细胞的生存能力。
DOI：
10.1016/j.canlet.2011.05.025
复制
发表时间：
2011-10-28
期刊：
影响因子：
9.7
通讯作者：
Fang, Jing
中科院分区：
文献类型：
--
作者：
Li, Xue-bing;Jiao, Shi;Fang, Jing
EAR2是鸡卵清蛋白上游启动子转录因子(COUP-TF)的成员。COUP-TF属于孤儿核受体，调节多种生物过程。人们对EAR2在癌症中的作用知之甚少，尽管在了解其他COUP-TF成员的功能方面已经取得了很大进展。本研究的目的是探讨EAR2在结直肠癌中的表达及其可能的功能。我们检测了EAR2在人类原发大肠恶性肿瘤及其配对的正常大肠组织中的表达。我们发现EAR2在大肠肿瘤中表达上调。EAR2基因敲除可诱导结肠癌细胞发生凋亡，提示EAR2可能具有调节结肠癌细胞生存能力的作用。体内肿瘤研究表明，EAR2基因的敲除抑制了结肠癌细胞的移植瘤生长。我们发现EAR2基因的敲除抑制了X连锁的凋亡抑制蛋白(XIAP)的表达，这表明EAR2至少部分地通过XIAP来调节细胞的存活率。在这篇论文中，我们证明了EAR2在结直肠癌中的表达增加，并且EAR2的敲除降低了结肠癌细胞的存活率和肿瘤的生长。我们的结果提示，EAR2在结直肠癌的发生发展中起着重要作用。研究结果还表明，EAR2可能成为结直肠癌的潜在治疗靶点。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
EAR2 is a member of the chick ovalbumin upstream promoter-transcription factors (COUP-TFs). COUP-TFs belong to orphan nuclear receptors and regulate many biological processes. Little is known regarding EAR2 in cancer, though much progress has been made in understanding the function of other COUP-TF members. The aim of this study is to investigate the expression and possible function of EAR2 in colorectal cancer. We determined expression of EAR2 in human primary colorectal malignant tumors and their paired adjacent normal colorectal tissues. We found that expression of EAR2 was upregulated in colorectal tumors. Knockdown of EAR2 induced apoptosis of colon cancer cells, suggesting that EAR2 may function to regulate survivability of colon cancer cells. In vivo tumor study demonstrated that knockdown of EAR2 inhibited the xenograft growth of colon cancer cells. We found that knockdown of EAR2 inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP), suggesting that EAR2 regulates cell survivability, at least partly, through XIAP. In this manuscript, we demonstrated that expression of EAR2 was elevated in colorectal cancer and knockdown of EAR2 reduced survivability and tumor growth of colon cancer cells. Our results suggest that EAR2 plays an important role in development of colorectal cancer. The findings also suggest that EAR2 may serve as a potential therapeutic target of colorectal cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.