title: Long noncoding RNA PVT1 indicates a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically regulating p15 and p16.
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.
authors.affiliation: Clinical Medical Examination Center, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, PR China. 31815857@qq.com.|Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China. 31815857@qq.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China. 273459189@qq.com.
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Cancer Research and Therapy Center, The Second Affiliated Hospital of Southeast University, Nanjing, 210029, Jiangsu, PR China. jsnydandan@sina.com.
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Yin
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, 210029, China. 991310547@qq.com.
authors.forename: Liang-hui
authors.initials: LH
authors.lastname: You
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. xutongpeng_njmu@163.com.
authors.forename: Tong-peng
authors.initials: TP
authors.lastname: Xu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. chenwenming_njmu@163.com.
authors.forename: Wen-ming
authors.initials: WM
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China. 854620993@qq.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan Road, Nanjing, 210011, Jiangsu, PR China. 411076921@qq.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China. 504997498@qq.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan Road, Nanjing, 210011, Jiangsu, PR China. zhaoxiawang88@hotmail.com.
authors.forename: Zhao-xia
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China. dewei@njmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Departments of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China. zhihongzhang1003@sina.com.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D057890:Epigenomics / Q000379:methods; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D014162:Transfection / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2