Abstract
BackgroundPancreatic ductal adenocarcinoma (PDAC) is still a lethal malignancy. Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. Here we identified overexpression of the lncRNA AFAP1-AS1 in PDAC patients and evaluated its prognostic and functional relevance.MethodsThe global lncRNA expression profile in PDAC was measured by lncRNA microarray. Expression of AFAP1-AS1 was evaluated by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) in 90 PDAC tissue samples and adjacent normal tissues. The impact of AFAP1-AS1 expression on cell proliferation, migration, and invasion were evaluated in vitro using knockdown and ectopic expression strategies.ResultsMicroarray analysis revealed that up-regulation of AFAP1-AS1 expression in PDAC tissues compared with normal adjacent tissues, which was confirmed by RT-qPCR in 69/90 cases (76.7%). Its overexpression was associated with lymph node metastasis, perineural invasion, and poor survival. When using AFAP1-AS1 as a prognostic marker, the areas under ROC curves were 0.8669 and 0.9370 for predicting tumor progression within 6 months and 1 year, respectively. In vitro functional experiments involving knockdown of AFAP1-AS1 resulted in attenuated PDAC cell proliferation, migration, and invasion. Ectopic expression of AFAP1-AS1 promoted cell proliferation, migration, and invasion.ConclusionsAFAP1-AS1 is a potential novel prognostic marker to predict the clinical outcome of PDAC patients after surgery and may be a rational target for therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0490-4) contains supplementary material, which is available to authorized users.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is still a lethal malignancy
Actin filament associated protein 1 (AFAP1)-AS1 is aberrantly overexpressed in human PDAC cell lines and cancerous tissues As a first attempt to identify differentially expressed long noncoding RNAs in two subtypes of PDAC tissues (PDAC patients with diabetes versus PDAC patients without diabetes), we conducted microarray analysis utilizing a microarray targeting 7419 LncRNAs using eight cases of PDAC tissues and four cases of chronic pancreatitis tissues (CP)
We noticed that the long noncoding RNA AFAP1-AS1 is one of the most up-regulated Long noncoding RNA (lncRNA) in both subtypes of PDAC tissues (Figure 1a), suggesting a potentially important role for AFAP1-AS1 in PDAC development
Summary
Pancreatic ductal adenocarcinoma (PDAC) is still a lethal malignancy. Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive human cancers [1]. PDAC is associated with a short survival that has been declining steadily since the early 1990s [2]. PDAC is characterized by a highly malignant phenotype that is associated with early metastasis and resistance to chemotherapy and radiation therapy [3]. Long noncoding RNAs (lncRNAs), which are defined as those longer than ~200 nucleotides but lacking protein coding capacity [3], have recently been shown to play a key role in regulating vital cellular functions including cancer progression [5]. Thousands of lncRNAs have been discovered through chromatin signature analysis and large-scale sequencing, and functional studies have shown that many of them
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