Abstract
BackgroundMounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the overall biological role and clinical significance of PVT1 in gastric carcinogenesis remains largely unknown.MethodsExpression of PVT1 was analyzed in 80 GC tissues and cell lines by qRT-PCR. The effect of PVT1 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Flow-cytometric analysis. GC cells transfected with shPVT1 were injected into nude mice to study the effect of PVT1 on tumorigenesis in vivo. RIP was performed to confirm the interaction between PVT1 and EZH2. ChIP was used to study the promoter region of related genes.ResultsThe higher expression of PVT1 was significantly correlated with deeper invasion depth and advanced TNM stage. Multivariate analyses revealed that PVT1 expression served as an independent predictor for overall survival (p = 0.031). Further experiments demonstrated that PVT1 knockdown significantly inhibited the proliferation both in vitro and in vivo. Importantly, we also showed that PVT1 played a key role in G1 arrest. Moreover, we further confirmed that PVT1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of p15 and p16. To our knowledge, this is the first report showed that the role and the mechanism of PVT1 in the progression of gastric cancer.ConclusionsTogether, these results suggest that lncRNA PVT1 may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0355-8) contains supplementary material, which is available to authorized users.
Highlights
Gastric cancer (GC) is the second leading cause of cancer death and the most common gastrointestinal malignancy in East Asia [1]
PVT1 expression is increased in human gastric cancer tissues and correlates with poor prognosis To investigate the role of PVT1 in gastric cancer progression, we detected the PVT1 expression levels in 80 paired gastric cancer tissues and corresponding non-tumor tissues by using qRT-PCR, and normalizing to GAPDH
The transcript levels of PVT1 were significantly up-regulated in 71.25% (57 of 80) cancerous tissues compared with adjacent non-tumor tissues (p < 0.01) (Figure 1A)
Summary
Gastric cancer (GC) is the second leading cause of cancer death and the most common gastrointestinal malignancy in East Asia [1]. Emerging evidence suggests that lncRNAs may play critical roles in cellular development, differentiation, and many other biological processes [3,4,5]. They have been shown to regulate gene expression at multiple levels, including chromatin modification, transcription and posttranscriptional processing. LncRNAs regulate gene transcription through recruiting transcription factors to their target gene promoters, activating gene expression [10]. They can block binding of transcription factors, potentially via formation of RNA-DNA-Triplexes [11]. Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. The overall biological role and clinical significance of PVT1 in gastric carcinogenesis remains largely unknown
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