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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Count
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Cell Proliferation
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Cyclin-Dependent Kinase 9 / genetics*
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Cyclin-Dependent Kinase 9 / metabolism
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Gene Expression Regulation
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HEK293 Cells
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HeLa Cells
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Humans
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Immunoprecipitation
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Primary Cell Culture
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Proto-Oncogenes
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA-Induced Silencing Complex / genetics*
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RNA-Induced Silencing Complex / metabolism
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Receptor, Notch2 / genetics*
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Receptor, Notch2 / metabolism
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Ribosomal Protein S6 Kinases, 90-kDa / genetics*
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism
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Signal Transduction
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Transfection
Substances
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MIRN191 microRNA, human
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MicroRNAs
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NOTCH2 protein, human
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RNA, Small Interfering
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RNA-Induced Silencing Complex
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Receptor, Notch2
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Ribosomal Protein S6 Kinases, 90-kDa
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ribosomal protein S6 kinase, 90kDa, polypeptide 3
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CDK9 protein, human
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Cyclin-Dependent Kinase 9