Reconstruction of microRNA/genes transcriptional regulatory networks of multiple myeloma through in silico integrative genomics analysis [PCL, gene]

The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.

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Calura E, Bisognin A, Manzoni M, Todoerti K, Taiana E, Sales G, Morgan GJ, Tonon G, Amodio N, Tassone P, Neri A, Agnelli L, Romualdi C, Bortoluzzi S