title: Identification of differentially expressed long noncoding RNAs in bladder cancer.
abstract: OBJECTIVE
  Loss of epigenetic gene regulation through altered long noncoding RNA (lncRNA) expression seems important in human cancer. LncRNAs have diagnostic and therapeutic potential, and offer insights into the biology disease, but little is known of their expression in urothelial cancer. Here, we identify differentially expressed lncRNAs with potential regulatory functions in urothelial cancer.
  
  
  METHODS
  The expression of 17,112 lncRNAs and 22,074 mRNAs was determined using microarrays in 83 normal and malignant urothelial (discovery) samples and selected RNAs with qPCR in 138 samples for validation. Significantly differentially expressed RNAs were identified and stratified according to tumor phenotype. siRNA knockdown, functional assays, and whole-genome transcriptomic profiling were used to identify potential roles of selected lncRNAs.
  
  
  RESULTS
  We observed upregulation of many lncRNAs in urothelial cancer that was distinct to corresponding, more balanced changes for mRNAs. In general, lncRNA expression reflected disease phenotype. We identified 32 lncRNAs with potential roles in disease progression. Focusing upon a promising candidate, we implicate upregulation of AB074278 in apoptosis avoidance and the maintenance of a proproliferative state in cancer through a potential interaction with EMP1, a tumor suppressor and a negative regulator of cell proliferation.
  
  
  CONCLUSIONS
  We report differential expression profiles for numerous lncRNA in urothelial cancer. We identify phenotype-specific expression and a potential mechanistic target to explain this observation. Further studies are required to validate lncRNAs as prognostic biomarkers in this disease.
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Peter
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Edyta
authors.initials: E
authors.lastname: Borkowska
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Drayton
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Callum P
authors.initials: CP
authors.lastname: Rakhit
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom. Department of Urology, University of Toronto, Toronto, Canada.
authors.forename: Aidan
authors.initials: A
authors.lastname: Noon
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Academic Urology Unit and Unit of Molecular Oncology, University of Sheffield, Sheffield, United Kingdom. j.catto@sheffield.ac.uk.
authors.forename: James Wf
authors.initials: JW
authors.lastname: Catto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger