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

Department of Medical Sciences, Leukemia Study Centre, University of Milan, Hematology 1-CTMO, Foundation IRCCS Policlinico, Milan, Italy.
Genes Chromosomes and Cancer (Impact Factor: 3.84). 04/2009; 48(6):521-31. DOI: 10.1002/gcc.20660
Source: PubMed

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 well-characterized 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.

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    ABSTRACT: Recent studies have revealed a pivotal role played by a class of small, noncoding RNAs, microRNA (miRNA), in multiple myeloma (MM), a plasma cell (PC) malignancy causing significant morbidity and mortality. Deregulated miRNA expression in patient's PCs and plasma has been associated with tumor progression, molecular subtypes, clinical staging, prognosis, and drug response in MM. A number of important oncogenic and tumor suppressor miRNAs have been discovered to regulate important genes and pathways such as p53 and IL6-JAK-STAT signaling. miRNAs may also form complex regulatory circuitry with genetic and epigenetic machineries, the deregulation of which could lead to malignant transformation and progression. The translational potential of miRNAs in the clinic is being increasingly recognized that they could represent novel biomarkers and therapeutic targets. This review comprehensively summarizes current progress in delineating the roles of miRNAs in MM pathobiology and management.
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    ABSTRACT: Background Recent studies have demonstrated that microRNA-22 (miR-22) was deregulated in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the clinical significance and prognostic value of miR-22 in epithelial ovarian cancer (EOC) haven¿t been investigated.Methods109 pairs of fresh EOC tissue and matched adjacent normal tissue specimens were collected between May 2007 and March 2013. Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-22. The chi-square test was used to assess miR-22 expression with respect to clinicopathological parameters. The survival curves of the patients were determined using the Kaplan-Meier method and Cox regression, and the log-rank test was used for statistical evaluations.ResultsmiR-22 expression in EOC tissues was significantly lower than that in matched normal adjacent tissues (mean¿±¿SD: 1.944¿±¿1.026 vs. 4.981¿±¿1.507, P¿<¿0.0001). Low miR-22 expression level was correlated with FIGO stage (P¿=¿0.006), tumor grade (P¿=¿0.03), and lymph node metastases (P¿=¿0.01). Kaplan-Meier analysis with the log-rank test indicated that low miR-22 expression had a significant impact on overall survival (44.4% vs. 64.5%; P¿=¿0.005) and progression-free survival (23.5% vs. 52.6%; P¿=¿0.004).Conclusions Our data demonstrated that the expression of miR-22 was downregulated in EOC, and associated with overall survival as well as progression-free survival, suggesting that miR-22 could serve as an efficient prognostic factor for EOC patients.Virtual SlidesThe virtual slide(s) for this article can be found here:
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