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Upregulated has-miR-4516 as a potential biomarker for early diagnosis of dust-induced pulmonary fibrosis in patients with pneumoconiosis
Toxicology Research ( IF 2.1 ) Pub Date : 2018-02-08 00:00:00 , DOI: 10.1039/c8tx00031j
Ruixue Huang 1, 2, 3, 4, 5 , Ting Yu 1, 2, 3, 4, 5 , Ying Li 4, 5, 6 , Jianan Hu 1, 2, 3, 4, 5
Affiliation  

Background: Pulmonary fibrosis (PF) is a representative pathological change in patients with pneumoconiosis; however, due to the absence of reliable and early biomarkers, microRNAs have recently emerged as potential candidates for identification. Objectives: The aim of our study was to discover the potential of PF-specific circulating microRNAs as early biomarkers among patients with pneumoconiosis. Methods: Four dust-exposed patients with PF and four matched healthy individuals (not exposed to dust) were recruited for the study. microRNA profiling was identified by micro-array and bioinformatics methods. Gene Ontology (GO) analysis was used to identify the potential biological or molecular processes modulated by these miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis was used to identify the potentially involved signaling pathways. miRNA-mRNA-binding network analysis was employed to identify genes potentially targeted by the miRNAs. Results: 1079 miRNAs were discovered, of which 406 were up-regulated and 117 were down-regulated in PF patients. 32 miRNAs were up-regulated by >4-fold and 17 miRNAs were down-regulated by >0.5 fold. GO analysis identified the biological processes affected by anatomical structure development, hemophilic cell adhesion and cell–cell adhesion via plasma membrane proteins. Target prediction software showed that serum has-miR-4516 targeted genes encoding basonuclin2, inhibitors of growth family member 4, the potassium voltage-gated channel, and “sha-1-related subfamily member 1” proteins. qRT-PCR revealed that has-miR-4516 was a potential biomarker of PF progression in patients with pneumoconiosis. Conclusions: Our findings suggest that the level of serum miR-4516 may be a potential biomarker for early diagnosis of PF in patients with pneumoconiosis. This is a pilot work that paves the way for a further functional study of the underlying regulatory mechanisms.

中文翻译:

上调的has-miR-4516可作为尘肺病患者尘埃诱发的肺纤维化早期诊断的潜在生物标志物

背景:肺纤维化(PF)是尘肺病患者的典型病理变化。然而,由于缺乏可靠和早期的生物标记,microRNA最近已成为潜在的鉴定候选物。目的:我们的研究目的是发现PF特异性循环微RNA作为尘肺病患者早期生物标志物的潜力。方法:招募了四名粉尘暴露的PF患者和四名相匹配的健康个体(未暴露于粉尘)进行研究。通过微阵列和生物信息学方法鉴定了microRNA谱。使用基因本体论(GO)分析来确定这些miRNA调控的潜在生物或分子过程。《京都议定书》的基因和基因组途径百科全书(KEGG)用于鉴定可能涉及的信号传导途径。使用miRNA-mRNA结合网络分析来鉴定miRNA可能靶向的基因。结果:发现了1079个miRNA,其中PF患者中有406个被上调,而117个被下调。32个miRNA上调了> 4倍,而17个miRNA下调了> 0.5倍。GO分析确定了受解剖结构发展,血友病细胞粘附和通过质膜蛋白引起的细胞间粘附影响的生物过程。目标预测软件显示,血清具有编码basonuclin2,生长家族成员4抑制剂,钾电压门控通道和“ sha-1相关亚家族成员1”蛋白的miR-4516靶向基因。qRT-PCR显示has-miR-4516是尘肺病患者PF进展的潜在生物标志物。结论:我们的研究结果表明,血清miR-4516的水平可能是尘肺病患者早期诊断PF的潜在生物标志物。这是一项试点工作,为进一步研究潜在的调节机制铺平了道路。
更新日期:2018-02-08
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