Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial cells, mainly due to former asbestos exposure. Little is known about the microRNA (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an essential role in the regulation of gene expression. This study was carried out to analyze the miRNA expression profile of 17 MM samples using miRNA microarray. The analysis distinguished the overall miRNA expression profiles of tumor tissue and normal mesothelium. Differentially expressed miRNAs were found in tumor samples compared with normal sample. Twelve of them, let-7b*, miR-1228*, miR-195*, miR-30b*, miR-32*, miR-345, miR-483-3p, miR-584, miR-595, miR-615-3p, and miR-885-3p, were highly expressed whereas the remaining nine, let-7e*, miR-144*, miR-203, miR-340*, miR-34a*, miR-423, miR-582, miR-7-1*, and miR-9, were unexpressed or had severely reduced expression levels. Target genes for these miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN, HGF, and PDGFA. Many of the miRNAs were located in chromosomal areas known to be deleted or gained in MM such as 8q24, 1p36, and 14q32. Furthermore, we could identify specific miRNAs for each histopathological subtype of MM. Regarding risk factors such as smoking status and asbestos exposure, significantly differentially expressed miRNAs were identified in smokers versus nonsmokers (miR-379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p), but not in asbestos-exposed patients versus nonexposed ones. This could be related to the method of assessment of asbestos exposure as asbestos remains to be the main contributor to the development of MM.

Lung cancer has the highest mortality rate of all of the cancers in the world and asbestos-related lung cancer is one of the leading occupational cancers. The identification of asbestos-related molecular changes has long been a topic of increasing research interest. The aim of this study was to identify novel asbestos-related molecular correlates by integrating miRNA expression profiling with previously obtained profiling data (aCGH and mRNA expression) from the same patient material. miRNA profiling was performed on 26 tumor and corresponding normal lung tissue samples from highly asbestos-exposed and non-exposed patients, and on eight control lung tissue samples. Data analyses on miRNA expression, and integration of miRNA and previously obtained mRNA data were performed using Chipster. A separate analysis was used to integrate miRNA and previously obtained aCGH data. Both known and new lung cancer-associated miRNAs and target genes with inverse correlation were discovered. Furthermore, DNA copy number alterations (e.g., gain at 12p13.31) were correlated with the deregulated miRNAs. Specifically, thirteen novel asbestos-related miRNAs (over-expressed: miR-148b, miR-374a, miR-24-1*, Let-7d, Let-7e, miR-199b-5p, miR-331-3p, and miR-96 and under-expressed: miR-939, miR-671-5p, miR-605, miR-1224-5p and miR-202) and inversely correlated target genes (e.g., GADD45A, LTBP1, FOSB, NCALD, CACNA2D2, MTSS1, EPB41L3) were identified. In addition, over-expression of the well known squamous cell carcinoma-associated miR-205 was linked to down-regulation of the DOK4 gene. The miRNAs/genes presented here may represent interesting targets for further investigation and could eventually have potential diagnostic implications.

The rare and highly aggressive adult soft tissue sarcomas leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) contain complex genomes characterized by a multitude of rearrangements, amplifications, and deletions. Differential diagnosis remains a challenge. MicroRNA (miRNA) profiling was conducted on a series of LMS and UPS samples to initially investigate the differential expression and to identify specific signatures useful for improving the differential diagnosis. Initially, 10 high-grade LMS and 10 high-grade UPS were profiled with a miRNA microarray. Two cultured human mesenchymal stem cell samples were used as controls. 38 and 46 miRNAs classified UPS and LMS samples, respectively, into separate groups compared to control samples. When comparing the two profiles, miR-199b-5p, miR-320a, miR-199a-3p, miR-126, miR-22 were differentially expressed. These were validated by RT-PCR on a further series of 27 UPS and 21 LMS for a total of 68 cases. The levels of miR-199-5p and miR-320a, in particular, confirmed the microarray data, the former highly expressed in UPS and the latter in LMS. Immunohistochemistry was performed on all 68 cases to confirm original diagnosis. Recently reported LMS- and UPS-associated genes were correlated with miRNA targets based on target algorithms of three databases. Several genes including IMP3, ROR2, MDM2, CDK4, and UPA, are targets of differentially expressed miRNAs. We identified miRNA expression patterns in LMS and UPS, linking them to chromosomal regions and mRNA targets known to be involved in tumor development/progression of LMS and UPS.