miR-144-3p是一种与严重糖皮质激素依赖性哮喘相关的生物标志物

2022/05/17

   摘要
   背景:MicroRNAs是一种非编码分子,既可作为表观遗传的调节因子,也可作为疾病(包括哮喘)的生物标志物。在个性化医疗时代,需要新的疾病相关生物标志物,可以帮助将疾病分类为表型,以进行治疗选择。目前,严重嗜酸性哮喘是临床实践中研究最广泛的表型之一,因为许多患者需要越来越高剂量的糖皮质激素,在某些情况下不能达到预期的结果。这类患者可能只能从生物制剂等替代药物中受益,因为这类药物需要新的生物标志物。
   目的:研究miR-144-3p的表达,以发现其是否可用作严重哮喘的诊断生物标志物。
   方法:我们在哮喘患者和健康个体的气道活检和血清中评估了miR-144-3p。在哮喘活检和转染miR-144-3p mimic的平滑肌细胞中研究mRNA。使用miRSystem、miRDB、STRING和ShinyGO 对miR-144-3p进行计算机调节以进行通路分析。
   结果:从我们的实验过程中,我们发现miR-144-3p是一个与哮喘严重程度和糖皮质激素治疗相关的生物标志物。MiR-144-3p在哮喘患者肺中增加,其存在与血液嗜酸性粒细胞增多以及气道中哮喘病理生理相关基因的表达直接相关。当在血清中研究时,这种miRNA在严重哮喘患者中增加,并与高剂量的糖皮质激素相关,因此使其成为以前使用高剂量糖皮质激素治疗的严重哮喘的潜在生物标志物。
   结论:miR-144-3p与哮喘患者呼吸道和血清中的严重疾病相关,并且这种关联与糖皮质激素治疗有关。

 
(中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校)
(Frontiers in Immunology 2022.13 DOI:10.3389/fimmu.2022.858722)

 
 
 
miR-144-3p Is a Biomarker Related to Severe Corticosteroid-Dependent Asthma
 
J. M. Rodrigo-Munoz, M. Gil-Martinez, C. Lorente-Sorolla, R. Garcia-Latorre, M.   Valverde-Monge, S. Quirce, et al.
 
Abstract
BACKGROUND:MicroRNAs are non-coding molecules that act both as regulators of the epigenetic landscape and as biomarkers for diseases, including asthma. In the era of personalized medicine, there is a need for novel disease-associated biomarkers that can help in classifying diseases into phenotypes for treatment selection. Currently, severe eosinophilic asthma is one of the most widely studied phenotypes in clinical practice, as many patients require higher and higher doses of corticosteroids, which in some cases fail to achieve the desired outcome. Such patients may only benefit from alternative drugs such as biologics, for which novel biomarkers are necessary.
OBJECTIVE:The objective of the study was to study the expression of miR-144-3p in order to discover its possible use as a diagnostic biomarker for severe asthma.
METHODS:For this purpose, miR-144-3p was evaluated in airway biopsies and serum from asthmatics and healthy individuals. mRNA was studied in asthmatic biopsies and smooth muscle cells transfected with miR-144-3p mimic. An in silico regulation of miR-144-3p was performed using miRSystem, miRDB, STRING, and ShinyGO for pathway analysis.
RESULTS:From our experimental procedures, we found that miR-144-3p is a biomarker associated with asthma severity and corticosteroid treatment. MiR-144-3p is increased in asthmatic lungs, and its presence correlates directly with blood eosinophilia and with the expression of genes involved in asthma pathophysiology in the airways. When studied in serum, this miRNA was increased in severe asthmatics and associated with higher doses of corticosteroids, thereby making it a potential biomarker for severe asthma previously treated with higher doses of corticosteroids. 
CONCLUSIONS:miR-144-3p is associated with severe diseases in both the airways and serum of asthmatics, and this association is related to corticosteroid treatment.
 


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