RNA结合蛋白作为氯福克酚药靶的机制初探

Preliminary study on the mechanism of RNA-binding protein as a drug target of clofoctol

目的探索氯福克酚靶向RNA结合蛋白的抗胶质瘤机制。方法Biotin pull-down实验检测RNA结合蛋白N-ras上游蛋白(UNR)与靶基因Krüppel样因子13(KLF13)mRNA各片段的结合,以及氯福克酚对UNR与下游靶基因KLF13 mRNA片段结合能力的影响;氯福克酚靶点稳定性的药物亲和反应(DARTS)样品质谱检测结果与转录组芯片分析相结合,筛选其他RNA结合蛋白作用靶点,并对其他下游靶基因进行预测分析。结果氯福克酚可以增强UNR与KLF13 mRNA片段的结合;氯福克酚还可与其他RNA结合蛋白相互作用,参与mTOR信号通路以及由肿瘤坏死因子相关凋亡诱导配体(TRAIL)激活的凋亡信号通路。结论氯福克酚可通过作用于RNA结合蛋白而起到抗胶质瘤的效果。

Objective To explore the molecular mechanism of anti-glioma by clofoctol targeting on RNA-binding proteins.Methods Biotin pull-down experiments were used to detect the binding of RNA-binding protein UNR(upstream of N-ras)to the target gene Krüppel-like factor 13(KLF13)mRNA fragments,and the effect of clofoctol on the binding to UNR to KLF13 mRNA fragments;The results of clofoctol DARTS sample's mass spectrometry combined with transcriptome chip analysis were used to screen other RNA-binding protein targets and to predict other downstream target genes.Results Clofoctol enhanced the interaction between UNR and the fragment of KLF13 mRNA;Clofoctol also acted on other RNA-binding proteins,and functioned in mTOR signaling pathway and TNF-related apoptosis-inducing ligand(TRAIL)-activated apoptotic signaling pathway.Conclusions Clofoctol can resist gliomas by acting on RNA-binding proteins.