EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression.
In this study, we examined the role of EHMT1 in embryonal rhabdomyosarcoma (ERMS), the most frequent subtype of RMS. We report that EHMT1 plays a key role in the migratory and invasive capacity of ERMS cells in vitro and in vivo. Transcriptomic analysis of EHMT1-depleted cells revealed significant alteration in cell migration and invasion pathways. SOX8, a transcription factor that has key roles in cellular motility was significantly decreased upon EHMT1 loss. Consistently, SOX8 depletion phenotypically mimicked EHMT1 loss. Moreover, RNA-Sequencing of SOX8 depleted cells showed down regulation of several integrin genes. Mechanistically, we show that EHMT1 upregulates SOX8 via regulation of BRD4 expression, and consequently its occupancy at the promoter. Our study reveals a novel EHMT1-SOX8 axis that mediates metastasis in ERMS. Overall design: RD cells were treated with [1] control siRNA (siscr) or EHMT1-specific siRNA (siEHMT1), [2] control siRNA (siscr) or SOX8-specific siRNA (siSOX8) for 48 hours, after which total RNA was collected with TRIzol reagent. RNA was purified and quality of purified RNA was checked using Nanodrop and gel electrophoresis. 3 samples of siscr and 3 samples of siEHMT1 were used for sequencing analysis, done by Novogene. 3 samples of siscr and 3 samples of siSOX8 were used for sequencing analysis, done by Novogene.