Identification of altered MicroRNA expression patterns in synovial sarcoma.

MicroRNAs (miRNAs) are noncoding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b, and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma. 2010 Wiley-Liss, Inc.