Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer
Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer
复制标题
长链非编码RNA HOTAIR的过度表达可预测上皮性卵巢癌患者的不良预后并促进肿瘤转移
DOI：
10.1016/j.ygyno.2014.03.556
复制
发表时间：
2014-07-01
影响因子：
4.7
通讯作者：
Hua, Ke-qin
中科院分区：
文献类型：
--
作者：
Qiu, Jun-jun;Lin, Ying-ying;Hua, Ke-qin
目标。尽管长非编码RNAs(Long Non-Coding RNAs，LncRNAs)正在成为癌症研究中的新的调节因子，但LncRNAs在上皮性卵巢癌(EOC)中的作用才刚刚开始研究。本研究以反义lncRNA HOX转录RNA(HOTAIR)为研究对象，探讨其在EOC中的表达模式、临床意义及生物学功能。检测卵巢癌组织中HOTAIR的表达，并分析其与临床病理因素及患者预后的关系。通过一系列的体外和体内实验，了解HOTAIR在卵巢癌转移中的作用。卵巢癌组织中HOTAIR表达升高，且与FIGO分期、肿瘤组织学分级、淋巴结转移、总生存期(OS)和无瘤生存期(DFS)呈高度正相关。多因素分析显示，HOTAIR表达是卵巢癌患者OS和DFS的独立预后因素。此外，体外实验结果表明，抑制HOTAIR在三种高转移EOC细胞系(SKOV3.ip1、H08910-PM和Hey-A8)中的表达显著减少细胞的迁移/侵袭。体内检测结果进一步证实了HOTAIR的促转移作用。此外，HOTAIR的促转移作用部分是通过调节某些基质金属蛋白酶(MMPs)和上皮向间充质转化(EMT)相关基因来实现的。我们的研究结果表明，HOTAIR在卵巢癌转移中起重要作用，可作为卵巢癌新的预后标志物和潜在的治疗靶点。(C)2014 Elsevier Inc.保留所有权利。
Objectives. Although long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in epithelial ovarian cancer (EOC) is just beginning to be studied. In this study, we focused on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression pattern, clinical significance, and biological function in EOC.Methods. HOTAIR expression in EOC tissues was examined and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of in vitro and in vivo assays were performed to understand the role of HOTAIR in EOC metastasis.Results. HOTAIR expression was elevated in EOC tissues, and HOTAIR levels were highly positively correlated with the FIGO stage, the histological grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that HOTAIR expression is an independent prognostic factor of OS and DFS in patients with EOC. Additionally, the results of in vitro assays showed that the suppression of HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1, H08910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results of in vivo assays further confirmed the pro-metastatic effects of HOTAIR. Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the regulation of certain matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT)-related genes.Conclusions. Our data suggest that HOTAIR plays a vital role in EOC metastasis and could represent a novel prognostic marker and potential therapeutic target in patients with EOC. (C) 2014 Elsevier Inc. All rights reserved..