The role of SMARCA1 in Rhabdomyosarcoma and Skeletal Muscle Differentiation

Division Of Basic Sciences - Nci

Investigators

Abstract

We used publicly available datasets to show that SMARCA1 is upregulated in PAX-fusion negative and positive rhabdomyosarcoma tissues compared to normal muscle. SMARCA1 knockout via CRISPR/Cas9 in the FP-RMS cell line RH30 induced marked downregulation of the transcription factors SNAI1 and SNAi2, as well as HDAC2. Phenotypic studies showed that SMARCA1 knockout FP-RMS cell lines showed a dramatic decrease in cell confluency and viability after trametinib treatment. Interestingly, trametinib increased SMARCA1 protein in FP-RMS cell lines. It was also found that SMARCA1 deletion reduced cell migration and prevented these cells from developing spheres, unlike control cells, which healed the migration gap and formed spheres. Gene clusters in RMS transcriptomic data showed that SMARCA1 co-expresses with RALA, a RAS effector. SMARCA1, in addition, is clustered with HDAC2. As demonstrated by co-immunoprecipitation, SMARCA1 and HDAC2 also interacted in RMS cells. This work will be continued by Dr. Judy Davie.