TY - JOUR
T1 - Disentangling the microRNA regulatory milieu in multiple myeloma
T2 - Integrative genomics analysis outlines mixed miRNATF circuits and pathway-derived networks modulated in t(4;14) patients
AU - Calura, Enrica
AU - Bisognin, Andrea
AU - Manzoni, Martina
AU - Todoerti, Katia
AU - Taiana, Elisa
AU - Sales, Gabriele
AU - Morgan, Gareth J.
AU - Tonon, Giovanni
AU - Amodio, Nicola
AU - Tassone, Pierfrancesco
AU - Neri, Antonino
AU - Agnelli, Luca
AU - Romualdi, Chiara
AU - Bortoluzzi, Stefania
PY - 2016
Y1 - 2016
N2 - The identification of overexpressed miRNAs in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. miRNA and gene expression profiles of two large representative MM datasets, available from retrospective and prospective series and encompassing a total of 249 patients at diagnosis, were analyzed by means of in silico integrative genomics methods, based on MAGIA2 and Micrographite computational procedures. We first identified relevant miRNA/transcription factors/target gene regulation circuits in the disease and linked them to biological processes. Members of the miR-99b/let-7e/miR-125a cluster, or of its paralog, upregulated in t(4;14), were connected with the specific transcription factors PBX1 and CEBPA and several target genes. These results were validated in two additional independent plasma cell tumor datasets. Then, we reconstructed a non-redundant miRNA-gene regulatory network in MM, linking miRNAs, such as let- 7g, miR-19a, mirR-20a, mir-21, miR-29 family, miR-34 family, miR-125b, miR-155, miR-221 to pathways associated with MM subtypes, in particular the ErbB, the Hippo, and the Acute myeloid leukemia associated pathways.
AB - The identification of overexpressed miRNAs in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. miRNA and gene expression profiles of two large representative MM datasets, available from retrospective and prospective series and encompassing a total of 249 patients at diagnosis, were analyzed by means of in silico integrative genomics methods, based on MAGIA2 and Micrographite computational procedures. We first identified relevant miRNA/transcription factors/target gene regulation circuits in the disease and linked them to biological processes. Members of the miR-99b/let-7e/miR-125a cluster, or of its paralog, upregulated in t(4;14), were connected with the specific transcription factors PBX1 and CEBPA and several target genes. These results were validated in two additional independent plasma cell tumor datasets. Then, we reconstructed a non-redundant miRNA-gene regulatory network in MM, linking miRNAs, such as let- 7g, miR-19a, mirR-20a, mir-21, miR-29 family, miR-34 family, miR-125b, miR-155, miR-221 to pathways associated with MM subtypes, in particular the ErbB, the Hippo, and the Acute myeloid leukemia associated pathways.
KW - Expression profiling
KW - MicroRNA
KW - Multiple myeloma
KW - T(4;14) translocation
KW - Transciptional regulatory network
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UR - http://www.scopus.com/inward/citedby.url?scp=84962266096&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6151
DO - 10.18632/oncotarget.6151
M3 - Article
AN - SCOPUS:84962266096
VL - 7
SP - 2367
EP - 2378
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 3
ER -