http://www.cnr.it/ontology/cnr/individuo/prodotto/ID189605

Identification of microRNA-regulated gene networks by expression analysis of target genes (Articolo in rivista)

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Identification of microRNA-regulated gene networks by expression analysis of target genes (Articolo in rivista) (literal)

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Gennarino V.A.; D'Angelo G.; Dharmalingam G.; Fernandez S.; Russolillo G.; Sanges R.; Mutarelli M.; Belcastro V.; Ballabio A.; Verde P.; Sardiello M.; Banfi S. (2012)
Identification of microRNA-regulated gene networks by expression analysis of target genes
in Genome research; Cold Spring Harbor Lab Press, Publications Dept., Woodbury (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Gennarino V.A.; D'Angelo G.; Dharmalingam G.; Fernandez S.; Russolillo G.; Sanges R.; Mutarelli M.; Belcastro V.; Ballabio A.; Verde P.; Sardiello M.; Banfi S. (literal)

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Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy CNAM, Lab Cedr, F-75141 Paris, France Chaire Stat Appl, F-75141 Paris, France Stn Zool A Dohrn, I-80121 Naples, Italy Texas Childrens Hosp, Baylor Coll Med, Dept Mol & Human Genet, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy Univ Naples 2, Dept Gen Pathol, I-80138 Naples, Italy (literal)

Titolo

Identification of microRNA-regulated gene networks by expression analysis of target genes (literal)

Abstract

MicroRNAs (miRNAs) and transcription factors control eukaryotic cell proliferation, differentiation, and metabolism through their specific gene regulatory networks. However, differently from transcription factors, our understanding of the processes regulated by miRNAs is currently limited. Here, we introduce gene network analysis as a new means for gaining insight into miRNA biology. A systematic analysis of all human miRNAs based on Co-expression Meta-analysis of miRNA Targets (CoMeTa) assigns high-resolution biological functions to miRNAs and provides a comprehensive, genome-scale analysis of human miRNA regulatory networks. Moreover, gene cotargeting analyses show that miRNAs synergistically regulate cohorts of genes that participate in similar processes. We experimentally validate the CoMeTa procedure through focusing on three poorly characterized miRNAs, miR-519d/190/340, which CoMeTa predicts to be associated with the TGF beta pathway. Using lung adenocarcinoma A549 cells as a model system, we show that miR-519d and miR-190 inhibit, while miR-340 enhances TGF beta signaling and its effects on cell proliferation, morphology, and scattering. Based on these findings, we formalize and propose co-expression analysis as a general paradigm for second-generation procedures to recognize bona fide targets and infer biological roles and network communities of miRNAs. (literal)

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