LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway
LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway
复制标题
LincRNA-ROR通过激活ZEB1通路促进胰腺癌侵袭、转移和肿瘤生长
DOI：
10.1016/j.canlet.2016.02.018
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发表时间：
2016-05-01
期刊：
影响因子：
9.7
通讯作者：
Hu, San-yuan
中科院分区：
文献类型：
--
作者：
Zhan, Han-xiang;Wang, Yao;Hu, San-yuan
胰腺癌(PC)仍然是最致命的恶性肿瘤之一，早期远处转移通常导致预后不良。最近的研究证实，长非编码RNA(Long Non-Coding RNAs，lncRNAs)在包括PC在内的恶性肿瘤的发生和转移中起着关键作用。然而，对于LincRNA-ROR(Linc-ROR)在PC中的作用却知之甚少。在本研究中，我们发现Linc-ROR在PC组织中表达上调。在体外和小鼠模型中，过表达Linc-ROR促进了细胞的增殖、迁移、侵袭和转移。反之，Linc-ROR基因敲除可减少肿瘤的增殖、侵袭和远处转移。从机制上，我们证实了Linc-ROR上调ZEB1，进而诱导上皮-间充质转化(EMT)，从而促进PC的侵袭性生物学行为。综上所述，这些结果表明Linc-ROR是ZEB1的重要调节因子，可以促进PC的侵袭和转移，可能是一种新的治疗靶点。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Pancreatic cancer (PC) remains one of the most lethal malignant tumors; early distant metastasis commonly results in poor prognosis. Recent studies confirmed the pivotal role of the long non-coding RNAs (lncRNAs) in tumorigenesis and metastasis of malignant tumors, including PC. However, little is known about the role of LincRNA-ROR (linc-ROR) in PC. In the present study, we found that linc-ROR was upregulated in PC tissues. Overexpression of linc-ROR promoted cells proliferation, migration, invasion and metastasis both in vitro and in a mouse model. Contrarily, knockdown of linc-ROR attenuated proliferation, invasion and distant metastasis. Mechanistically, we confirmed that linc-ROR up-regulates ZEB1 and then induces epithelial-mesenchymal transition (EMT), which promotes the aggressive biological behaviors of PC. Together, these results indicate that linc-ROR acts as an important regulator of ZEB1, can promote invasion and metastasis in PC, and may represent a novel therapeutic target. (C) 2016 Elsevier Ireland Ltd. All rights reserved.