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Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs.
Respiratory Research ( IF 4.7 ) Pub Date : 2020-01-10 , DOI: 10.1186/s12931-019-1257-x
Yifang Liao 1 , Ping Li 2 , Yanxia Wang 3 , Hong Chen 4 , Shangwei Ning 3 , Dongju Su 4
Affiliation  

BACKGROUND Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. METHODS Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. RESULTS This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). CONCLUSIONS The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.

中文翻译:

与哮喘相关的竞争性内源RNA网络的构建揭示了新颖的长非编码RNA和潜在的新药。

背景技术哮喘是一种以慢性气道炎症为特征的异质性疾病。长的非编码RNA可以作为竞争性内源RNA与mRNA竞争,并在许多疾病中发挥重要作用。然而,关于哮喘中长非编码RNA和与长非编码RNA相关的竞争性内源RNA网络的概况知之甚少。在当前的研究中,我们旨在探讨哮喘患者中长期存在的非编码RNA-microRNA-mRNA竞争性内源性RNA网络及其对治疗和预后的潜在影响。方法从基因表达综合数据库下载与哮喘相关的基因表达谱,并用这些基因重新注释,并鉴定与哮喘相关的差异表达mRNA和长非编码RNA。使用starBase数据库下载长期的非编码RNA-miRNA相互作用数据和mRNA-miRNA相互作用数据,以构建长期的非编码RNA-miRNA-mRNA全球竞争内源RNA网络,并提取与哮喘相关的差异表达竞争内源RNA网络。最后,进行了与哮喘相关的差异表达竞争内源RNA网络的功能富集分析和药物重新定位,以进一步鉴定关键的长非编码RNA和与哮喘相关的潜在疗法。结果本研究构建了与哮喘相关的竞争性内源RNA网络,确定了5个关键的长非编码RNA(MALAT1,MIR17HG,CASC2,MAGI2-AS3,DAPK1-IT1),并鉴定了8种潜在的新药(他莫昔芬,鲁索替尼,维甲酸,槲皮素) ,达沙替尼,左卡尼汀,尼氟酸,格列本脲)。结论结果提示长非编码RNA在哮喘中起重要作用,这些新颖的长非编码RNA可能是潜在的治疗靶标和预后生物标志物。同时,通过药物重新定位技术发现了潜在的哮喘治疗新药,为哮喘的治疗提供了新的方向。
更新日期:2020-01-11
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