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Open Access 01-12-2015 | Research

Long noncoding RNA PVT1 indicates a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically regulating p15 and p16

Authors: Rong Kong, Er-bao Zhang, Dan-dan Yin, Liang-hui You, Tong-peng Xu, Wen-ming Chen, Rui Xia, Li Wan, Ming Sun, Zhao-xia Wang, Wei De, Zhi-hong Zhang

Published in: Molecular Cancer | Issue 1/2015

Abstract

Background

Mounting 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.

Methods

Expression 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.

Results

The 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.

Conclusions

Together, these results suggest that lncRNA PVT1 may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

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Title: Long noncoding RNA PVT1 indicates a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically regulating p15 and p16
Authors: Rong Kong
Er-bao Zhang
Dan-dan Yin
Liang-hui You
Tong-peng Xu
Wen-ming Chen
Rui Xia
Li Wan
Ming Sun
Zhao-xia Wang
Wei De
Zhi-hong Zhang
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-015-0355-8

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