title: miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.
abstract: BACKGROUND
  Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information.
  
  
  METHODS
  We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods.
  
  
  RESULTS
  We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process.
  
  
  CONCLUSIONS
  This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.
authors.affiliation: Division of Surgery and Cancer, Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Enerly
authors.forename: Israel
authors.initials: I
authors.lastname: Steinfeld
authors.forename: Kristine
authors.initials: K
authors.lastname: Kleivi
authors.forename: Suvi-Katri
authors.initials: SK
authors.lastname: Leivonen
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Aure
authors.forename: Hege G
authors.initials: HG
authors.lastname: Russnes
authors.forename: Jo Anders
authors.initials: JA
authors.lastname: Rønneberg
authors.forename: Hilde
authors.initials: H
authors.lastname: Johnsen
authors.forename: Roy
authors.initials: R
authors.lastname: Navon
authors.forename: Einar
authors.initials: E
authors.lastname: Rødland
authors.forename: Rami
authors.initials: R
authors.lastname: Mäkelä
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.forename: Merja
authors.initials: M
authors.lastname: Perälä
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D046911:Macromolecular Substances / Q000032:analysis / Q000378:metabolism; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018511:Systems Integration; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D054928:Validation Studies as Topic
chemical_list: D046911:Macromolecular Substances; D035683:MicroRNAs; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53