Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer
Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer
复制标题
长非编码 RNA GAPLINC 调节 CD44 依赖性细胞侵袭性并与胃癌不良预后相关
DOI：
10.1158/0008-5472.can-14-0686
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发表时间：
2014-12-01
期刊：
影响因子：
11.2
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
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作者：
Hu, Ye;Wang, Jilin;Fang, Jing-Yuan
长链非编码RNA（lncRNA）在肿瘤发生中的作用越来越明显。在这项研究中，我们报告的结果涉及一种新的lncRNA在胃癌，称为GAPLINC（胃腺癌预测长基因间非编码RNA），基于使用全球微阵列和原位杂交（ISH）分析，以确定异常表达lncRNA在人类胃癌标本。GAPLINC是一种924 bp长的lncRNA，在胃癌组织中高度表达。GAPLINC抑制和胃癌细胞中的基因表达谱揭示了细胞迁移途径的改变，其中CD 44表达的相关性最高。操纵GAPLINC表达改变了CD 44 mRNA丰度，GAPLINC对细胞迁移和增殖的影响通过抑制CD 44表达而被中和。机制研究表明，GAPLINC调节CD 44作为miR 211 - 3 p的分子诱饵，miR 211 - 3 p是一种靶向CD 44和GAPLINC的microRNA。组织ISH分析表明，GAPLINC过表达定义了一个生存率极低的胃癌患者亚组。综上所述，我们的研究结果确定了CD 44癌基因的非编码调控途径，为胃癌细胞的侵袭性提供了新的依据。(C)2014年AACR。
It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression profiling in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness. (C) 2014 AACR.