title: Profiling and functional analyses of microRNAs and their target gene products in human uterine leiomyomas.
abstract: BACKGROUND
  Human uterine leiomyomas (ULM) are characterized by dysregulation of a large number of genes and non-coding regulatory microRNAs. In order to identify microRNA::mRNA associations relevant to ULM pathogenesis, we examined global correlation patterns between the altered microRNA expression and the predicted target genes in ULMs and matched myometria.
  
  
  RESULTS
  Patterns of inverse association of microRNA with mRNA expression in ULMs revealed an involvement of multiple candidate pathways, including extensive transcriptional reprogramming, cell proliferation control, MAP kinase, TGF-beta, WNT, JAK/STAT signaling, remodeling of cell adhesion, and cell-cell and cell-matrix contacts. We further examined the correlation between the expression of the selected target gene protein products and microRNAs in thirty-six paired sets of leiomyomas and matched myometria. We found that a number of dysregulated microRNAs were inversely correlated with their targets at the protein level. The comparative genomic hybridization (CGH) in eight ULM patients revealed that partially shared deletions of two distinct chromosomal regions might be responsible for loss of cancer-associated microRNA expression and could thus contribute to the ULM pathogenesis via deregulation of target mRNAs. Last, we functionally tested the repressor effects of selected cancer-related microRNAs on their predicted target genes in vitro.
  
  
  CONCLUSIONS
  We found that some but not all of the predicted and inversely correlated target genes in ULMs can be directly regulated by microRNAs in vitro. Our findings provide a broad overview of molecular events underlying the tumorigenesis of uterine ULMs and identify select genetic and regulatory events that alter microRNA expression and may play important roles in ULM pathobiology by positively regulating tumor growth while maintaining the non-invasive character of ULMs.
authors.affiliation: Department of Pathology, School of Medicine, New York University, New York, New York, United States of America.
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Huihui
authors.initials: H
authors.lastname: Ye
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.forename: JingJing
authors.initials: J
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Patricia
authors.initials: P
authors.lastname: Soteropoulos
authors.forename: Gokce A
authors.initials: GA
authors.lastname: Toruner
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D023281:Genomics; D006706:Homeostasis; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D035683:MicroRNAs; D011506:Proteins; D012333:RNA, Messenger
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