title: miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing.
abstract: BACKGROUND
  The pathways regulating the transition of mammalian cells from quiescence to proliferation are mediated by multiple miRNAs. Despite significant improvements in our understanding of miRNA targeting, the majority of miRNA regulatory networks are still largely unknown and require experimental validation.
  
  
  RESULTS
  Here we identified miR-503, miR-103, and miR-494 as negative regulators of proliferation in primary human cells. We experimentally determined their genome wide target profiles using RNA-induced silencing complex (RISC) immunoprecipitations and gene expression profiling. Analysis of the genome wide target profiles revealed evidence of extensive regulation of gene expression through non-canonical target pairing by miR-503. We identified the proto-oncogene DDHD2 as a target of miR-503 that requires pairing outside of the canonical 5' seed region of miR-503, representing a novel mode of miRNA-target pairing. Further bioinformatics analysis implicated miR-503 and DDHD2 in breast cancer tumorigenesis.
  
  
  CONCLUSIONS
  Our results provide an extensive genome wide set of targets for miR-503, miR-103, and miR-494, and suggest that miR-503 may act as a tumor suppressor in breast cancer by its direct non-canonical targeting of DDHD2.
authors: Department of Molecular Biosciences, Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA. damon.polioudakis@gmail.com.
authors: Damon
authors: D
authors: Polioudakis
authors: Department of Molecular Biosciences, Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA. abell.nathan@gmail.com.
authors: Nathan S
authors: NS
authors: Abell
authors: Department of Molecular Biosciences, Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA. vishy.iyer@gmail.com.
authors: Vishwanath R
authors: VR
authors: Iyer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas
chemical_list: C000715470:MAS1 protein, human; C544749:MIRN103 microRNA, human; C547168:MIRN494 microRNA, human; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D010740:Phospholipases; C541017:DDHD2 protein, human
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