Abstract 5350: Distinction of childhood soft tissue sarcomas with high metastatic potential by miRNAs

Abstract

Abstract Background: Advanced stage alveolar (RMA) and embryonal rhabdomyosarcoma (RME) as well as malignant rhabdoid tumor (MRT) have a poor prognosis. Novel treatment approaches based on an improved understanding of metastatic invasion are required. Aberrant microRNA (miRNA) expression is found in cancer progression and metastatic invasion and may help to identify novel targets. The aim of this study was to identify specific miRNA expression patterns in pediatric soft tissue sarcomas. Methods: We analyzed the expression of 743 miRNAs in 5 RMA, RME, and MRT formalin fixed tissue samples and in the rhabdomyosarcoma (RMS) cell lines Rh30 and RD using an Illumina BeadArray. Differentially expressed miRNAs between RMS and MRT specimens were identified on the basis of the cubic spline algorithm using BeadStudio Software. Selected target miRNAs were transfected with mimic or inhibitor oligonucleotides. Functional analysis was monitored by western blotting, flow cytometry, and migration assays. Results: Principal component analysis as well as Spearman's rank correlation on the set of differentially expressed miRNAs showed tissue-specific clustering. A review of the literature revealed 23 miRNAs promoting and 46 miRNAs suppressing metastatic invasion. Eight miRNAs regulating migration in both directions were also described. In our study, metastatic invasion associated miRNAs miR-9* and miR-221 were overexpressed in RMS tissue samples compared to MRT. miR-200c, which inhibits metastatic invasion, was lower expressed in RMS than in MRT. Transient transfection of RMS cells with a miR-200c mimic resulted neither in a reduction of the direct target ZEB1 nor in an increase of the ZEB1-repressed ectopic E-cadherin expression. Migration of RMS cells after induction of miR-200c was not decreased. Furthermore, inhibition of miR-9* and miR-221 in RMS cell lines did not influence migration characteristics. Conclusions: Pediatric RMS and MRT can be distinguished by their specific miRNA expression pattern. These might also help for an optimized risk stratification of these tumors. A modulation of the metastatic invasion was not possible by the investigated miRNAs. Therefore, regulation of migration seems to be controlled by multiple miRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5350. doi:10.1158/1538-7445.AM2011-5350