MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes

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...

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Vydané v:	PloS one Ročník 10; číslo 5; s. e0126535
Hlavní autori:	Polioudakis, Damon, Abell, Nathan S., Iyer, Vishwanath R.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 20.05.2015 Public Library of Science (PLoS)
Predmet:	Angiogenesis Apoptosis Brain cancer Breast cancer Cancer Cell Count Cell cycle Cell growth Cell Proliferation Cyclin-Dependent Kinase 9 - genetics Cyclin-Dependent Kinase 9 - metabolism Fibroblasts Fibroblasts - cytology Fibroblasts - metabolism Gene expression Gene Expression Regulation Genetic aspects Genomes HEK293 Cells HeLa Cells Humans Identification Immunoprecipitation Kinases Lymphoma Mammals MicroRNA MicroRNAs MicroRNAs - antagonists & inhibitors MicroRNAs - genetics MicroRNAs - metabolism Molecular biology Nucleotide sequence Oncogenes Physiological aspects Physiology Primary Cell Culture Proteins Proto-Oncogenes Receptor, Notch2 - genetics Receptor, Notch2 - metabolism Ribonucleic acid Ribosomal Protein S6 Kinases, 90-kDa - genetics Ribosomal Protein S6 Kinases, 90-kDa - metabolism RNA RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA-Induced Silencing Complex - genetics RNA-Induced Silencing Complex - metabolism RNA-mediated interference Signal Transduction Stem cells Synthetic biology Target recognition Thyroid gland Transfection Tumorigenesis Wound healing United States
ISSN:	1932-6203, 1932-6203
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: DP VRI. Performed the experiments: DP NSA. Analyzed the data: DP NSA. Wrote the paper: DP VRI. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0126535