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Blood First Edition Paper, prepublished online October 21, 2009; DOI 10.1182/blood-2009-08-237495.
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Submitted August 13, 2009; accepted September 24, 2009.

Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma

Marta Lionetti1, Marta Biasiolo2, Luca Agnelli1, Katia Todoerti1, Laura Mosca1, Sonia Fabris1, Gabriele Sales2, Giorgio Lambertenghi Deliliers1, Silvio Bicciato3, Luigia Lombardi1, Stefania Bortoluzzi2 and Antonino Neri1,4

1 Department of Medical Sciences, University of Milan, Hematology 1-CTMO, Foundation IRCCS Policlinico, Milan, Italy; 2 Laboratory of Computational Biology, Department of Biology, University of Padua, Padua, Italy; 3 Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy

* Corresponding author; email: antonino.neri{at}unimi.it

Abstract

To date, little evidence of miRNA expression/deregulation in multiple myeloma (MM) has been reported. To characterize miRNA in the context of the major MM molecular types, we generated miRNA expression profiles of highly-purified malignant plasma cells from 40 primary tumors. Furthermore, transcriptional profiles, available for all patients, were used to investigate the occurrence of miRNA/predicted target mRNA pairs anti-correlations, and the miRNA and genome-wide DNA data were integrated in a subset of patients to evaluate the influence of allelic imbalances on miRNA expression. Differential miRNA expression patterns were identified which were mainly associated with the major IGH translocations: particularly, t(4;14) patients showed specific over-expression of let-7e, miR-125a-5p and miR-99b belonging to a cluster at 19q13.33. The occurrence of other lesions, i.e. 1q gain, 13q and 17p deletions, and hyperdiploidy, was slightly characterized by specific miRNA signatures. Furthermore, the occurrence of several allelic imbalances or loss-of-heterozygosity was found significantly associated with the altered expression of miRNAs located in the involved regions, such as let-7b at 22q13.31 or miR-140-3p at 16q22. Finally, the integrative analysis based on computational target prediction and miRNA/mRNA profiling defined a network of putative functional miRNA-target regulatory relations supported by expression data.


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