Department of Orthopaedics, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong 266035, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4291-4298. doi: 10.3892/mmr.2018.8418. Epub 2018 Jan 10.
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 α2 chain, N‑myc proto‑oncogene and transforming growth factor β1, 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.
环吡酮胺(CPX)是一种合成抗真菌药物,主要用于治疗皮肤真菌病。本研究旨在确定 CPX 是否会影响尤文肉瘤的进展。本研究表明,CPX 治疗可能通过尤文肉瘤断点区域 1-友白血病整合 1(EWS-FLI1)抑制尤文肉瘤(ES)的进展,EWS-FLI1 是 ES 患者中常见的融合转录本结构。为了确定 ES 进展的潜在机制,对来自基因表达综合数据库的三个高通量基因组或转录组数据集进行了交叉分析。结果表明,CPX 可能通过影响血管发育和 DNA 复制来抑制 ES 的生长。全基因组表达和结合谱的组合分析揭示了 CPX 在 ES 中的几个潜在靶点,包括Ⅰ型胶原α2 链、N- myc 原癌基因和转化生长因子β1,这些靶点包含 FLI1 的显著富集结合峰。此外,网络分析,包括蛋白质-蛋白质相互作用网络和转录调控网络,提供了 CPX 在 ES 中的作用的进一步详细信息。本研究可为 ES 的治疗提供新的解决方案,并可能有助于改善其预后。