mRNA-seq of PTC-028 treated fusion-positive rhabdomyosarcoma cells

Purpose: This study aims to identify novel targets in the rare pediatric cancer, fusion-positive rhabdomyosarcoma (FP-RMS), and examine differences/similarities in FP-RMS tumor responses to BMI1 (B lymphoma Mo-MLV insert region 1 homolog) inhibition. Methods: FP-RMS cell lines Rh28 and Rh30 were treated with DMSO (vehicle) or PTC-028, a BMI1 inhibitor, and RNA was collected after 24 or 48 hr in triplicate. RNA-seq was performed, and gene expression data were analyzed through Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses. Data from OncoPPi and the STRING database were also utilized in this study. Results: Both Rh28 and Rh30 had some overlapping pathways affected by PTC-028, notably downregulation of cell cycle progression, the DNA damage response, and cholesterol biosynthesis. Rh30+PTC-028 had more genes containing TEAD-motifs downregulated compared to Rh28+PTC-028. Rh28 and Rh30 also had differing changes in expression in kinases of LATS1/2, EPHA2, and PDGFRA. Conclusion: Overall, these results bring new insights into pathways influenced by BMI1 expression and contrasting intertumor drug responses in FP-RMS. Overall design: Fusion-positive rhabdomyosarcoma cell lines (Rh28 and Rh30) were treated with either DMSO (24 hr) or PTC-028 (24 hr or 48 hr). Total RNA was extracted from DMSO and PTC-028 treated cells. Cells were analyzed by RNA-seq in triplicate.