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首页> 外文期刊>Scientific reports. >Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma
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Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma

机译：构建Circrna / miRNA / mRNA调节网络，探讨透明细胞肾细胞癌的潜在发病机制和治疗选择

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Clear cell renal cell carcinoma (ccRCC) is the most representative subtype of renal cancer. CircRNA acts as a kind of ceRNA to play a role in regulating microRNA (miRNA) in many cancers. However, the potential pathogenesis role of the regulatory network among circRNA/miRNA/mRNA is not clear and has not been fully explored. CircRNA expression profile data were obtained from GEO datasets, and the differentially expressed circRNAs (DECs) were identified through utilizing R package (Limma) firstly. Secondly, miRNAs that were regulated by these circRNAs were predicted by using Cancer-specific circRNA database and Circular RNA Interactome. Thirdly, some related genes were identified by intersecting targeted genes, which was predicted by a web tool (miRWalk) and differentially expressed genes, which was obtained from TCGA datasets. Function enrichment was analyzed, and a PPI network was constructed by Cytoscape software and DAVID web set. Subsequently, ten hub-genes were screened from the network, and the overall survival time in patients of ccRCC with abnormal expression of these hub-genes were completed by GEPIA web set. In the last, a circRNA/miRNA/mRNA regulatory network was constructed, and potential compounds and drug which may have the function of anti ccRCC were forecasted by taking advantage of CMap and PharmGKB datasets. Six DECs (hsa_circ_0029340, hsa_circ_0039238, hsa_circ_0031594, hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were obtained and six miRNAs (miR-1205, miR-657, miR-587, miR-637, miR-1278, miR-548p) which are regulated by three circRNAs (hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were also predicted. Then 497 overlapped genes regulated by these six miRNAs above had been predicted, and function enrichment analysis revealed these genes are mainly linked with some regulation functions of cancers. Ten hub-genes (PTGER3, ADCY2, APLN, CXCL5, GRM4, MCHR1, NPY5R, CXCR4, ACKR3, MTNR1B) have been screened from a PPI network. PTGER3, ADCY2, CXCL5, GRM4 and APLN were identified to have a significant effect on the overall survival time of patients with ccRCC. Furthermore, one compound (josamycin) and four kinds of drugs (capecitabine, hmg-coa reductase inhibitors, ace Inhibitors and bevacizumab) were confirmed as potential therapeutic options for ccRCC by CMap analysis and pharmacogenomics analysis. This study implies the potential pathogenesis of the regulatory network among circRNA/miRNA/mRNA and provides some potential therapeutic options for ccRCC.
机译：透明细胞肾细胞癌（CCRCC）是肾癌最具代表性的亚型。 Circrna作为一种Cerna，在许多癌症中调节microRNA（miRNA）中发挥作用。然而，CircRNA / miRNA / mRNA之间的调控网络的潜在发病机制不明确，并未完全探索。通过Geo数据集获得Circrna表达谱数据，并且通过首先利用R包（Limma）来识别差异表达的Circrnas（DECS）。其次，通过使用癌症特异性循环数据库和圆形RNA互联蛋白来预测由这些CircRNA调节的miRNA。第三，通过交叉靶向基因鉴定一些相关基因，其由腹板工具（miRWALK）和差异表达基因预测，其从TCGA数据集获得。分析了功能丰富，通过Cytoscape软件和David Web集构建了PPI网络。随后，从网络中筛选十个中心基因，通过Gepia网集完成了CCRCC患者的总存活时间，并且通过Gepia Web组完成了这些轮毂基因的异常表达。在最后，通过利用CMAP和PharmGKB数据集预测，构建了CircrNA / miRNA / mRNA调节网络，并且可以通过CMAP和PharmgKB数据集预测可能具有抗CCRCC功能的潜在化合物和药物。获得六个DECS（HSA_CIRC_0029340，HSA_CIRC_0039238，HSA_CIRC_0031594，HSA_CIRC_0084927，HSA_CIRC_00354927，HSA_CIRC_0035427，HSA_CIRC_0025135），并六个MIRNA（MIR-1205，MIR-657，MIR-587，MIR-637，MIR-1278，MIR-548P），其受到三个CircRNA（HSA_CIRC_0084927，HSA_CIRC_0035442，HSA_CIRC_0025135）也被预测。然后预测了由此六个miRNA调节的497个重叠基因，并且功能富集分析显示这些基因主要与一些癌症的调控功能相关联。已经从PPI网络筛选了十个集线器（PTINGE3，ADCY2，APLN，CXCL5，GRM4，MCHR1，NPY5R，CXCR4，ACKR3，MTNR1B）。鉴定PTING3，ADCY2，CXCL5，GRM4和APLN对CCRCC患者的整体存活时间产生显着影响。此外，通过CMAP分析和药癌组学分析证实了一种化合物（Capecitcin）和四种药物（Capecitabine，HMG-CoA还原酶抑制剂，ACE抑制剂和Bevacizumab）是CCRCC的潜在治疗选择。本研究暗示CircrNA / miRNA / mRNA中调控网络的潜在发病机制，为CCRCC提供了一些潜在的治疗方法。

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