Combined analysis of gene expression and genome binding profiles identified potential therapeutic targets of ciclopirox in Ewing sarcoma

摘要

Ciclopirox (CPX) is a synthetic antifungal drug that is mainly used to treat dermatomycoses. The aim of the present study was to determine whether CPX could influence Ewing sarcoma progression. The present study suggested that CPX treatment may inhibit Ewing sarcoma (ES) progression through Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWS-FLI1), a common fusion transcript structure in patients with ES. To determine the underlying mechanisms of ES progression, cross analysis was conducted on three high-throughput genome or transcript me datasets from the Gene Expression Omnibus. The results indicated that CPX may inhibit ES growth by affecting vasculature development and DNA replication. A combination of genome-wide expression and binding profiles revealed several potential targets for CPX in ES, including collagen type I 2 chain, N-myc proto-oncogene and transforming growth factor 1, which contained significantly enriched binding peaks of FLI1. In addition, network analysis, including a protein-protein interaction network and a transcription regulatory network, provided further detailed information about the roles of CPX in ES. This study may provide a novel solution for ES treatment and may also aid in improving its prognosis.