Failure to downregulate the BAF53a subunit of the SWI/SNF chromatin remodelling complex contributes to the differentiation block in rhabdomyosarcoma

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children and young adults, is characterized by a partially differentiated myogenic phenotype. We have previously shown that block of tumor growth and resumption of differentiation can be achieved by re-expression of miR-206, a muscle-enriched microRNA missing in RMS. In this work we focused on BAF53a, one of the genes downregulated in miR-206-expressing RMS cells, which codes for a subunit of the SWI/SNF chromatin remodeling complex. Here we show that the BAF53a transcript is significantly higher in primary RMS tumors than in normal muscle, and is a direct target of miR-206. Sustained expression of BAF53a interferes with differentiation in myogenic cells, while its silencing in RMS cells increases expression of myogenic markers and inhibits proliferation and anchorage-independent growth. Accordingly, BAF53a silencing also impairs ERMS and ARMS tumor growth, inducing their morphological and biochemical differentiation. These results indicate that failure to downregulate the BAF53a subunit may contribute to the pathogenesis of RMS, and suggest that BAF53a may represents a novel therapeutic target for this tumor.