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

作者：Calura Enrica; Bisognin Andrea; Manzoni Martina; Todoerti Katia; Taiana Elisa; Sales Gabriele; Morgan Gareth J; Tonon Giovanni; Amodio Nicola; Tassone Pierfrancesco; Neri Antonino; Agnelli Luca^*; Romualdi Chiara; Bortoluzzi Stefania

来源：Oncotarget, 2016, 7(3): 2367-2378.

DOI：10.18632/oncotarget.6151

• multiple myeloma
• transciptional regulatory network
• t(4
• 14) translocation
• microRNA
• expression profiling

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.

• 出版日期2016-1-19