Disentangling the microRNA regulatory milieu in multiple myeloma: Integrative genomics analysis outlines mixed miRNATF circuits and pathway-derived networks modulated in t(4;14) patients

Enrica Calura, Andrea Bisognin, Martina Manzoni, Katia Todoerti, Elisa Taiana, Gabriele Sales, G. Morgan, Giovanni Tonon, Nicola Amodio, Pierfrancesco Tassone, Antonino Neri, Luca Agnelli, Chiara Romualdi, S. Bortoluzzi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2367-2378
Number of pages12
JournalOncotarget
Volume7
Issue number3
DOIs
Publication statusPublished - 2016

Keywords

  • Expression profiling
  • MicroRNA
  • Multiple myeloma
  • T(4;14) translocation
  • Transciptional regulatory network

ASJC Scopus subject areas

  • Oncology

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