Role of EHMT1 in Alveolar Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma, wherein the malignant tumors arise from the myoblast like cells due to the perturbations in growth and differentiation. Alveolar rhabdomyosarcoma (ARMS) is one of the two major histological subtypes which exhibits high metastatic potential and tumor recurrence culminating in poor prognosis. In the recent past, understanding the epigenetic modifications in these tumors with less genetic alterations has shed light on the process of tumor pathogenesis and development of potential epi-drugs for the effective treatment strategies. Epigenetic regulator, Euchromatin histone lysine methyltransferase 1 (EHMT1)/G9A-like protein (GLP) and its homolog Euchromatin histone lysine methyltransferase 1 (EHMT2)/G9A has been shown to promote proliferation and inhibit differentiation in the mouse myoblast cells, independently. Also, previous study from our lab reported the overexpression of EHMT2 and molecular mechanism associated with the oncogenic phenotype in ARMS. However, expression pattern and functional role of EHMT1 in ARMS is unknown. Herein, we investigated the role of EHMT1 in ARMS. Our preliminary data indicated the overexpression of EHMT1 and the associated oncogenic phenotypes in ARMS. Although EHMT1 has shown to be upregulated and correlated with the increased disease severity in several cancers including gastric, esophagus, squamous cell carcinoma, ovarian and breast cancer, the mechanism involved in the EHMT1 mediated tumorigenesis was unclear. Therefore, through our current study we aimed to understand the expression pattern and the mechanism through which EHMT1 regulated cancer phenotypes in ARMS, for this we performed whole transcriptomic analysis in ARMS cell lines upon EHMT1 knockdown for the first time. In addition, we also compared the expression levels of EHMT1 between Human skeletal muscle myoblasts (HSMM) and ARMS patient samples (obtained from St Jude cloud database). We examined the differentially expressed genes upon EHMT1/GLP knockdown in ARMS cell line, to identify potential downstream targets of EHMT1. Triplicates for each conditions are used in the current study. Also, RNA expression of EHMT1 is compared between HSMM and ARMS patient tumor samples (n=32) from St. Jude cloud's genomic database (https://platform.stjude.cloud/data/diseases)