Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12857/115793
Title: Expanding the repertoire of miRNAs and miRNA-offset RNAs expressed in multiple myeloma by small RNA deep sequencing
Authors: Agnelli, Luca
Bisognin, Andrea 
Todoerti, Katia
Manzoni, Martina
Taiana, Elisa
Galletti, Serena
Cutrona, Giovanna
Gaffo, Enrico 
Bortoluzzi, Stefania 
Neri, Antonino
Keywords Plus: MICRORNA EXPRESSION;GENE-MUTATIONS;COMPENDIUM;DISCOVERY
Mesh headings: MicroRNAs;Multiple Myeloma;Transcriptome
Secondary Mesh headings: Biomarkers, Tumor;Computational Biology;Gene Expression Profiling;Gene Expression Regulation, Neoplastic;High-Throughput Nucleotide Sequencing;Humans;Prognosis;Reproducibility of Results
Issue Date: 2019
Publisher: NATURE PUBLISHING GROUP
Journal: Blood cancer journal 
Abstract: 
Microarray analysis of the multiple myeloma (MM) miRNome has unraveled the differential expression of miRNAs in cytogenetic subgroups, their involvement in the tumor biology and their effectiveness in prognostic models. Herein, the small RNA transcriptional landscape in MM has been investigated exploiting the possibilities offered by small RNA-seq, including accurate quantification of known mature species, discovery and characterization of isomiRs, and miRNA-offset RNAs (moRNAs). Matched small RNA-seq and miRNA GeneChip® microarray expression profiles were obtained in a representative panel of 30 primary MM tumors, fully characterized for genomic aberrations and mutations. RNA-seq and microarray gave concordant estimations of known species. Enhanced analysis of RNA-seq data with the miR&moRe pipeline led to the characterization of 655 known and 17 new mature miRNAs and of 74 moRNAs expressed in the considered cohort, 5 of which (moR-150-3p, moR-24-2-5p, moR-421-5p, moR-21-5p, and moR-6724-5p) at high level. Ectopic expression of miR-135a-3p in t(4;14) patients, upregulation of moR-150-3p and moR-21-5p in t(14;16)/t(14;20) samples, and of moR-6724-1-5p in patients overexpressing CCND1 were uncovered and validated by qRT-PCR. Overall, RNA-seq offered a more complete overview of small non-coding RNA in MM tumors, indicating specific moRNAs that demand further investigations to explore their role in MM biology.
URI: http://hdl.handle.net/20.500.12857/115793
ISSN: 2044-5385
DOI: 10.1038/s41408-019-0184-x
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