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.
Highlights
Gastric cancer is the second leading cause of cancer-related mortality in the world, and the majority of patients with gastric cancer are diagnosed at an advanced stage and die within 24 months after operation because of recurrence and metastasis [1, 2]
As the alteration of gene expression is often associated with copy number variations (CNV) in cancers, we tested whether CNV is prevalent in deregulated long noncoding RNAs (lncRNA) in gastric cancer
The genomic regions with CNV in gastric cancers were obtained from the Cancer Genome Atlas (TCGA) dataset, and re-assigned to lncRNA gene loci using the CNTools algorithm
Summary
Gastric cancer is the second leading cause of cancer-related mortality in the world, and the majority of patients with gastric cancer are diagnosed at an advanced stage and die within 24 months after operation because of recurrence and metastasis [1, 2]. To improve gastric cancer early diagnosis and targeted therapy, an in-depth understanding of molecular underpinnings of the disease is required [3,4,5]. It is of clinical importance to identify genes that contribute to gastric cancer development and present predictive value for diagnosis or prognosis [6,7,8]. Most reported potential biomarkers for gastric cancer are protein-coding genes (PCG), including the novel somatic gene targets (ARID1A, FAT4, MLL, and KMT2C) revealed by large-scale cancer genomic studies. Despite extensive efforts to develop PCG-based biomarkers, only modest. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
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