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Integrated analysis of microRNAs, transcription factors and target genes expression discloses a specific molecular architecture of hyperdiploid multiple myeloma

2015; Impact Journals LLC; Volume: 6; Issue: 22 Linguagem: Inglês

10.18632/oncotarget.4302

1949-2553

Maria Teresa Di Martino, Pietro Hiram Guzzi, Daniele Caracciolo, Luca Agnelli, Antonino Neri, Brian A. Walker, Gareth J. Morgan, Mario Cannataro, Pierfrancesco Tassone, Pierosandro Tagliaferri,

PI3K/AKT/mTOR signaling in cancer

// Maria Teresa Di Martino 1,* , Pietro Hiram Guzzi 2,* , Daniele Caracciolo 1 , Luca Agnelli 3 , Antonino Neri 3 , Brian A. Walker 4 , Gareth J. Morgan 5 , Mario Cannataro 2 , Pierfrancesco Tassone 1,6,* and Pierosandro Tagliaferri 1,* 1 Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy 2 Department of Surgical and Medical Sciences, University of Catanzaro, Catanzaro, Italy 3 Department of Clinical Sciences and Community Health, University of Milan, Hematology1 CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy 4 Centre for Molecular Pathology, The Royal Marsden Hospital, London, UK 5 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA 6 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA * These authors have contributed equally to this work Correspondence to: Maria Teresa Di Martino, email: // Keywords : integromics, microRNA, miRNA, transcription factors, multiple myeloma, hyperdiploid myeloma Received : March 23, 2015 Accepted : May 13, 2015 Published : May 27, 2015 Abstract Multiple Myeloma (MM) is a malignancy characterized by the hyperdiploid (HD-MM) and the non-hyperdiploid (nHD-MM) subtypes. To shed light within the molecular architecture of these subtypes, we used a novel integromics approach. By annotated MM patient mRNA/microRNA (miRNA) datasets, we investigated mRNAs and miRNAs profiles with relation to changes in transcriptional regulators expression. We found that HD-MM displays specific gene and miRNA expression profiles, involving the Signal Transducer and Activator of Transcription (STAT)3 pathway as well as the Transforming Growth Factor–beta (TGFβ) and the transcription regulator Nuclear Protein-1 (NUPR1). Our data define specific molecular features of HD-MM that may translate in the identification of novel relevant druggable targets.