Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro

Synovial sarcoma is a highly aggressive soft tissue sarcoma characterized by the presence of the fusion oncogene SS18-SSX. It is believed that SS18-SSX may either disrupt the SWI/SNF complex’s inhibition of the polycomb complex 2 (PRC2) methyltransferase, Enhancer of Zeste Homologue 2 (EZH2), or directly recruit PRC2 to silence target genes abnormally. This has significant therapeutic implications, as several small molecule inhibitors of EZH2 are now entering early phase clinical trials. In this study, we first confirmed that 76% of human synovial sarcoma samples express EZH2. We then explored the potential of targeting EZH2 as a therapeutic approach in vitro. Using shRNA or siRNA to knock down EZH2 led to reduced cell growth and migration in various synovial sarcoma cell lines. Similarly, the selective EZH2 inhibitor EPZ005687 inhibited cell proliferation and migration. These findings suggest that targeting EZH2 could be an effective treatment strategy for synovial sarcoma, with clinical trials currently enrolling patients.