Integrative high-resolution microarray analysis of human myeloma cell lines reveals deregulated miRNA expression associated with allelic imbalances and gene expression profiles

Marta Lionetti, Luca Agnelli, Laura Mosca, Sonia Fabris, Adrian Andronache, Katia Todoerti, Domenica Ronchetti, Giorgio Lambertenghi Deliliers, Antonino Neri

Research output: Contribution to journalArticlepeer-review

Abstract

It is thought that altered microRNA (miRNA) expression due to various mechanisms plays a critical role in the pathogenesis of most human cancers. Notably, about half of the known miRNAs are intragenic and frequently coexpressed with their host genes. To date there is little evidence concerning miRNA expression in multiple myeloma (MM). In an attempt to provide insights into miRNA deregulation in MM, we profiled global miRNA expression in a panel of molecularly wellcharacterized human myeloma cell lines (HMCLs) using high-resolution microarrays, and then used integrative analyses to identify altered patterns correlated with DNA copy number (CN) or gene expression profiles. We identified 16 miRNAs mapped to chromosomal regions frequently involved in numerical imbalances in MM, whose expression significantly correlated with the CN of the corresponding miRNA genes; among these, miR-22 expression was also affected by chromosome arm 17p loss in a representative panel of primary MM tumors. The expression of 32 intronic miRNAs significantly correlated with that of their host transcripts, some of which were highly deregulated in MM patients. The expression of some of the miRNAs was validated by quantitative RT-PCR. Finally, a number of the identified miRNAs have previously been reported to play important roles in tumorigenesis. Overall, our data highlight that genomic alterations may significantly affect miRNA expression in HMCLs and demonstrate a frequent coexpression of intronic miRNAs with their host genes that may have a pathogenetic relevance in plasma cell transformation.

Original languageEnglish
Pages (from-to)521-531
Number of pages11
JournalGenes Chromosomes and Cancer
Volume48
Issue number6
DOIs
Publication statusPublished - Jun 2009

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Medicine(all)

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