BACKGROUND: The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to 
be fully elucidated. To identify miRNAs that are potentially deregulated in MM, 
we investigated those mapping within transcription units, based on evidence that 
intronic miRNAs are frequently coexpressed with their host genes. To this end, 
we monitored host transcript expression values in a panel of 20 human MM cell 
lines (HMCLs) and focused on transcripts whose expression varied significantly 
across the dataset.
METHODS: miRNA expression was quantified by Quantitative Real-Time PCR. Gene 
expression and genome profiling data were generated on Affymetrix 
oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was 
used to investigate differentially expressed transcripts. Conventional 
statistics were used to test correlations for significance. Public libraries 
were queried to predict putative miRNA targets.
RESULTS: We identified transcripts specific to six miRNA host genes (CCPG1, 
GULP1, EVL, TACSTD1, MEST, and TNIK) whose average changes in expression varied 
at least 2-fold from the mean of the examined dataset. We evaluated the 
expression levels of the corresponding intronic miRNAs and identified a 
significant correlation between the expression levels of MEST, EVL, and GULP1 
and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, 
respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased 
expression of the three host genes and their corresponding intronic miRNAs was 
not correlated with local copy number variations. Notably, miRNAs and their host 
genes were overexpressed in a fraction of primary tumors with respect to normal 
plasma cells; however, this finding was not correlated with known molecular 
myeloma groups. The predicted putative miRNA targets and the transcriptional 
profiles associated with the primary tumors suggest that MEST/miR-335 and 
EVL/miR-342-3p may play a role in plasma cell homing and/or interactions with 
the bone marrow microenvironment.
CONCLUSION: Our data support the idea that intronic miRNAs and their host genes 
are regulated dependently, and may contribute to the understanding of their 
biological roles in cancer. To our knowledge, this is the first evidence of 
deregulated miRNA expression in MM, providing insights that may lead to the 
identification of new biomarkers and altered molecular pathways of the disease.