Format

Send to

Choose Destination
Cancer Res. 2014 Dec 1;74(23):6890-902. doi: 10.1158/0008-5472.CAN-14-0686. Epub 2014 Oct 2.

Long noncoding RNA GAPLINC regulates CD44-dependent cell invasiveness and associates with poor prognosis of gastric cancer.

Author information

1
State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China.
3
Department of Surgery, University of Michigan, Ann Arbor, Michigan.
4
State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jiexu@yahoo.com jingyuanfang@yahoo.com.

Abstract

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.

PMID:
25277524
DOI:
10.1158/0008-5472.CAN-14-0686
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center