title: A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer.
abstract: In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth in vivo.
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Statistics, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA.
authors.forename: Sihai D
authors.initials: SD
authors.lastname: Zhao
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Youyou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Stem Biology and Tissue Engineering, Department of Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jean
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, University of Turin, Turin 10124, Italy.
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kathleen T
authors.initials: KT
authors.lastname: Montone
authors.affiliation: Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.affiliation: Department of Systems Biology, MD Anderson Cancer Center, Houston, TX 7705, USA.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Genome Institute, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Systems Biology, MD Anderson Cancer Center, Houston, TX 7705, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: linzhang@mail.med.upenn.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D055550:Protein Stability; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000502:physiology*; D059467:Transcriptome; D047368:Tumor Burden
chemical_list: C069077:BMI1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D062085:RNA, Long Noncoding; D063150:Polycomb Repressive Complex 1