title: MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.
abstract: miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Damon
authors.initials: D
authors.lastname: Polioudakis
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Abell
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Vishwanath R
authors.initials: VR
authors.lastname: Iyer
mesh_terms: D002452:Cell Count; D049109:Cell Proliferation; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011519:Proto-Oncogenes; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics* / Q000378:metabolism; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: C546177:MIRN191 microRNA, human; D035683:MicroRNAs; C497764:NOTCH2 protein, human; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D051883:Receptor, Notch2; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9