Abstract A33: Histone demethylase KDM3A in rhabdomyosarcoma

Abstract

Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, adolescents, and young adults, presenting a myogenic phenotype. RMS can be divided into two major histopathologic subtypes: driver oncofusion (PAX3/7-FOXO1) positive, alveolar (ARMS), and oncofusion-negative embryonal (ERMS). Histone methylation is a key element of chromatin-based modifications that regulates a number of cellular processes, including DNA replication, DNA repair, and gene transcription. Histone demethylase gene family members (HDMs) regulate gene expression by removing methyl marks on histone tails to activate or repress transcription. KDM3A (lysine-specific demethylase 3A or JMJD1A) is a histone demethylase belonging to the Jumonji C-terminal domain (JmjC)-containing histone demethylases that selectively removes mono- and dimethyl groups from H3K9. It has been demonstrated that KDM3A is overexpressed in many kinds of cancer, such as bladder, lung, and breast cancer, and, previously shown by our laboratory, in Ewing sarcoma, contributing to carcinogenesis. We and others have identified KDM3A as overexpressed in RMS, but the functional consequences of this overexpression have not been examined. The aim of this study was to analyze the influence of KDM3A on RMS biology. Two different RMS cells lines were used, RH30 (ARMS) and RD (ERMS), to perform stable shRNA-mediated KDM3A knockdown. The protein and RNA levels were analyzed by Western blotting and RT-qPCR, respectively. The phenotypic effects of KDM3A knockdown were analyzed by proliferation assays (MTT and clonogenic assay) and cell migration (transwell migration assay). KDM3A knockdown was able to inhibit the proliferation, colony formation, and migration of RMS cell lines, demonstrating an important role in RMS biology. Citation Format: Lays M. Sobral, Paul Jedlicka. Histone demethylase KDM3A in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A33.