RT Journal
A1 Volinia, Stefano
A1 Galasso, Marco
A1 Costinean, Stefan
A1 Tagliavini, Luca
A1 Gamberoni, Giacomo
A1 Drusco, Alessandra
A1 Marchesini, Jlenia
A1 Mascellani, Nicoletta
A1 Sana, Maria Elena
A1 Abu Jarour, Ramzey
A1 Desponts, Caroline
A1 Teitell, Michael
A1 Baffa, Raffaele
A1 Aqeilan, Rami
A1 Iorio, Marilena V.
A1 Taccioli, Cristian
A1 Garzon, Ramiro
A1 Di Leva, Gianpiero
A1 Fabbri, Muller
A1 Catozzi, Marco
A1 Previati, Maurizio
A1 Ambs, Stefan
A1 Palumbo, Tiziana
A1 Garofalo, Michela
A1 Veronese, Angelo
A1 Bottoni, Arianna
A1 Gasparini, Pierluigi
A1 Harris, Curtis C.
A1 Visone, Rosa
A1 Pekarsky, Yuri
A1 de la Chapelle, Albert
A1 Bloomston, Mark
A1 Dillhoff, Mary
A1 Rassenti, Laura Z.
A1 Kipps, Thomas J.
A1 Huebner, Kay
A1 Pichiorri, Flavia
A1 Lenze, Dido
A1 Cairo, Stefano
A1 Buendia, Marie-Annick
A1 Pineau, Pascal
A1 Dejean, Anne
A1 Zanesi, Nicola
A1 Rossi, Simona
A1 Calin, George A.
A1 Liu, Chang-Gong
A1 Palatini, Jeff
A1 Negrini, Massimo
A1 Vecchione, Andrea
A1 Rosenberg, Anne
A1 Croce, Carlo M.
T1 Reprogramming of miRNA networks in cancer and leukemia
JF Genome Research 
JO Genome Research 
YR 2010 
FD May 01 
VO 20 
IS 5 
SP 589 
OP 599 
DO 10.1101/gr.098046.109 
UL http://genome.cshlp.org/content/20/5/589.abstract 
AB We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network.