Nt Popov, Ds Minchev, Mm Naydenov, In Minkov, Ti Vachev
State Psychiatry Hospital Pazardzhik, Pazardzik, Bulgaria.
Department of Plant Physiology and Molecular Biology, University of Plovdiv "Paisii Hilendarski," Plovdiv, Plovdiv, Bulgaria.
Balkan J Med Genet. 2018 Dec 31;21(2):5-12. doi: 10.2478/bjmg-2018-0026. eCollection 2018 Dec.
Circulating microRNAs (miRNAs) are emerging as promising diagnostic biomarkers for autism spectrum disorder (ASD), but their usefulness for detecting ASD remains unclear. Nowadays, development of promising biomarkers for ASD remains a challenge. Recently, dysregulation of the miRNAs expression in postmortem brain tissue, serum and peripheral blood, have been associated with ASD. Circulating miRNAs are known to be secreted by a number of different cells and can interpose delivery of information into receiver cells, thus affecting their functions. Based on this fact, it is supposed that serum miRNAs could be a novel class of biomarkers for prognosis or diagnosis of pathological disorders including ASD. In the current research, we investigated whether the expression patterns of circulating miRNAs showed dysregulation in subjects diagnosed with ASD. Expression levels of serum miR-328-3p and miR-3135a were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) method of subjects diagnosed with ASD in comparison with healthy control subjects. Our data showed that miR-328-3p and miR-3135a were substantially down-regulated in ASD patients than in those of healthy control subjects. Moreover, target gene analysis of altered serum miRNAs displayed that these molecules targeted 162 genes denoted as unique validated targets in the miRWalk database, 71 of which appear to participate in biological pathways involved in synaptic pathways and neurodegenerative condition such as Alzheimer, Huntington and Parkinson diseases. Finally, the results strongly suggested that dys-regulated serum miRNAs might be involved in molecular pathways associated with ASD and miR-328-3p and miR-3135a have the potential to be promising novel biomarkers for ASD.
循环微RNA(miRNA)正逐渐成为自闭症谱系障碍(ASD)颇具前景的诊断生物标志物,但其在检测ASD方面的效用仍不明确。如今,开发有前景的ASD生物标志物仍是一项挑战。最近,死后脑组织、血清和外周血中miRNA表达失调与ASD有关。已知循环miRNA由多种不同细胞分泌,可将信息传递至受体细胞,从而影响其功能。基于这一事实,推测血清miRNA可能是包括ASD在内的病理疾病预后或诊断的新型生物标志物类别。在当前研究中,我们调查了被诊断为ASD的受试者中循环miRNA的表达模式是否失调。通过定量逆转录聚合酶链反应(qRT-PCR)方法分析了被诊断为ASD的受试者与健康对照受试者血清中miR-328-3p和miR-3135a的表达水平。我们的数据显示,与健康对照受试者相比,ASD患者中miR-328-3p和miR-3135a显著下调。此外,对血清中改变的miRNA进行靶基因分析显示,这些分子靶向miRWalk数据库中标记为独特验证靶点的162个基因,其中71个基因似乎参与了与突触途径和神经退行性疾病(如阿尔茨海默病、亨廷顿病和帕金森病)相关的生物途径。最后,结果强烈表明,血清miRNA失调可能参与了与ASD相关的分子途径,并且miR-328-3p和miR-3135a有潜力成为ASD颇具前景的新型生物标志物。