a systematic screen reveals microrna clusters that significantly regulate four major signaling pathways系统屏幕显示microrna集群,显著调节四个主要信号通路.pdfVIP

A Systematic Screen Reveals MicroRNA Clusters That Significantly Regulate Four Major Signaling Pathways 1. 2. 2 3 4 1 Lindsey E. Becker , Zhongxin Lu , Weiqun Chen , Wei Xiong , Maiying Kong , Yong Li * 1 Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America, 2 Department of Medical Laboratory and Central Laboratory, The Central Hospital of Wuhan, Wuhan, Hubei, China, 3 Cancer Research Institute, Central South University, Changsha, Hunan, China, 4 Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky, United States of America 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-kB, 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 pathwa