Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer

被引：242

作者：

Hu, Ye ^{[1
,2
]}

Wang, Jilin ^{[1
,2
]}

Qian, Jin ^{[3
]}

Kong, Xuan ^{[1
,2
]}

Tang, Jieting ^{[1
,2
]}

Wang, Yingchao ^{[1
,2
]}

Chen, Haoyan ^{[3
]}

Hong, Jie ^{[3
]}

Zou, Weiping ^{[4
]}

Chen, Yingxuan ^{[1
,2
]}

Xu, Jie ^{[1
,2
]}

Fang, Jing-Yuan ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai 200001, Peoples R China

[2] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Div Gastroenterol & Hepatol, Shanghai 200001, Peoples R China

[3] Minist Hlth, Shanghai Inst Digest Dis, Key Lab Gastroenterol & Hepatol, Shanghai, Peoples R China

[4] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

来源：

CANCER RESEARCH | 2014年 / 74卷 / 23期

基金：

中国国家自然科学基金;

关键词：

EXPRESSION PROFILES; TUMOR-SUPPRESSOR; MUTANT P53; PROLIFERATION; PROGRESSION; METASTASIS; TISSUE; MODEL; CIS;

D O I：

10.1158/0008-5472.CAN-14-0686

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：6890 / 6902

页数：13

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