title: A systematic screen reveals MicroRNA clusters that significantly regulate four major signaling pathways.
abstract: MicroRNAs (miRNAs) are encoded in the genome as individual miRNA genes or as gene clusters transcribed as polycistronic units. About 50% of all miRNAs are estimated to be co-expressed with neighboring miRNAs. Recent studies have begun to illuminate the importance of the clustering of miRNAs from an evolutionary, as well as a functional standpoint. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. This cooperative method of targeting could produce effects on an overall process that are much more dramatic than the smaller effects often associated with regulation by an individual miRNA. In this study, we screened 366 human miRNA minigenes to determine their effects on the major signaling pathways culminating in AP-1, NF-κB, c-Myc, or p53 transcriptional activity. By stratifying these data into miRNA clusters, this systematic screen provides experimental evidence for the combined effects of clustered miRNAs on these signaling pathways. We also verify p53 as a direct target of miR-200a. This study is the first to provide a panoramic view of miRNA clusters' effects on cellular pathways.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY, USA.
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Becker
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Lu
authors.forename: Weiqun
authors.initials: W
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Maiying
authors.initials: M
authors.lastname: Kong
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D008156:Luciferases