XXXX -dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes.

@entity1 @entity9976 @entity19 @entity15977 @entity344 @entity1129 @entity2855
BACKGROUND _ AIMS: Smooth muscle cells (SMCs) change phenotypes under various pathophysiological conditions. These changes are largely controlled by the @entity2855 ( @entity2855 ), a transcription factor that binds to CC ( @entity1129 )6 GG (CArG) boxes in SM contractile genes. MicroRNAs (miRNA) regulate transitions among @entity9976 phenotypes. The @entity9976 miRNA transcriptome ( @entity9976 miRNAome) and its regulation by @entity2855 have not been determined. METHODS: We performed massively parallel sequencing to identify gastrointestinal (GI) @entity9976 miRNA transcriptomes in @entity19 and @entity1 . @entity9976 miRNA transcriptomes were mapped to identify all CArG boxes, which were confirmed by @entity2855 knockdown and microarrays. Quantitative polymerase chain reaction was used to identify @entity9976 -phenotypic miRNAs in differentiated and proliferating SMCs. Bioinformatics and target validation analysis showed regulation of @entity9976 phenotype by @entity2855 -dependent, @entity9976 -phenotype miRNAs. RESULTS: We cloned and identified GI miRNA transcriptomes using genome-wide analyses of @entity19 and @entity1 cells. The SM miRNAome consisted of hundreds of unique miRNAs that were highly conserved among both species. We mapped miRNAs CArG boxes and found that many had an @entity2855 -dependent signature in the SM miRNAome. The SM miRNAs CArG boxes had several distinct features. We also identified approximately 100 @entity9976 -phenotypic miRNAs that were induced in differentiated or proliferative @entity9976 phenotypes. We showed that @entity2855 -dependent, @entity9976 -phenotypic miRNAs bind and regulate @entity2855 and its cofactors, myocadin (Myocd) and member of ETS oncogene family @entity15977 . CONCLUSIONS: The @entity344 phenotypes are controlled by @entity2855 -dependent, @entity9976 -phenotypic miRNAs that regulate expression of @entity2855 , MYOCD, and @entity15977 .
