title: A Positive Feedback Loop of lncRNA-PVT1and FOXM1 Facilitates Gastric Cancer Growth and Invasion.
abstract: Purpose:The long, noncoding RNA (lncRNA)PVT1is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms ofPVT1in gastric cancer tumorigenesis and progression.Experimental Design:The expression level ofPVT1was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions ofPVT1were assessed byin vitroandin vivofunctional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify thePVT1-interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 andPVT1Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on thePVT1promoter.Results:The lncRNAPVT1was significantly upregulated in gastric cancer tissues compared with ANTs. High expression ofPVT1predicted poor prognosis in patients with gastric cancer.PVT1enhanced gastric cancer cell proliferation and invasionin vitroandin vivoPVT1directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover,PVT1is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to thePVT1promoter to activate its transcription. Finally,PVT1fulfilled its oncogenic functions in a FOXM1-mediated manner.Conclusions:Our study suggests thatPVT1promotes tumor progression by interacting with FOXM1.PVT1may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop ofPVT1-FOXM1 could be a therapeutic target in pharmacologic strategies.Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Mi-Die
authors.initials: MD
authors.lastname: Xu
authors.affiliation: Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qi
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Qiongyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Ni
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Wanrun
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Hangzhou Canhelp Genomics Company Limited, Hangzhou, Zhejiang, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pathology, First Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, First Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. dx2008cn@163.com shengweiqi2006@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. dx2008cn@163.com shengweiqi2006@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Pathology, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D018572:Disease-Free Survival; D025461:Feedback, Physiological; D000072278:Forkhead Box Protein M1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D013058:Mass Spectrometry; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding