Expanding the repertoire of miRNAs and miRNA-offset RNAs expressed in multiple myeloma by small RNA deep sequencing

L. Agnelli, A. Bisognin, K. Todoerti, M. Manzoni, E. Taiana, S. Galletti, G. Cutrona, E. Gaffo, S. Bortoluzzi, A. Neri

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number21
JournalBlood Cancer Journal
Issue number3
Publication statusPublished - 2019


  • genomic RNA
  • microRNA
  • microRNA 135a 3p
  • microRNA offset RNA
  • microRNA offset RNA 150 3p
  • microRNA offset RNA 21 5p
  • microRNA offset RNA 24 2 p
  • microRNA offset RNA 421 5p
  • microRNA offset RNA 6724 5p
  • small untranslated RNA
  • unclassified drug
  • Article
  • clinical article
  • ectopic expression
  • human
  • microarray analysis
  • multiple myeloma
  • protein expression
  • RNA analysis
  • RNA sequence
  • upregulation


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