title: Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer.
abstract: Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.
authors.affiliation: Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai 200433, China.|Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.|Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Hacisuleyman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.|Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
authors.forename: Teng
authors.initials: T
authors.lastname: Fei
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.|Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.|Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Mary Gwo-Shu
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Harvard Medical School, Boston, Massachusetts 02215, USA.|Department of Medicine Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.|Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D015153:Blotting, Western; D002458:Cell Fractionation; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks; D045325:HCT116 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D011471:Prostatic Neoplasms / Q000235:genetics*; D034443:RNA Transport / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; C000598536:TUG1 long noncoding RNA, human; D063151:Polycomb Repressive Complex 2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human