Identification of miRnas with possible prognostic roles for HAM/TSP

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.人类T细胞嗜淋巴细胞病毒1型（Human T-cell lymphotropic virus type 1, HTLV-1）相关性脊髓病/热带痉挛性截瘫（HAM/TSP）是一种隐匿进展的脊髓疾病，目前尚无有效治疗手段。学界对开发可预测HAM/TSP发病机制的潜在生物标志物抱有极大研究兴趣。本研究采用Illumina大规模并行测序（Massive Parallel Sequencing, MPS）技术，分析了HAM/TSP患者（n=10）、无症状HTLV-1感染者（ASP，n=8）以及第二组健康对照者（n=5）的细胞全局非编码RNA组表达谱。研究借助多种生物信息学工具，对小RNA（small RNA, sRNA）-MPS测序读段进行比对、注释与表达谱分析。相较于健康对照（HC）组，在HAM组与ASP组共检测到402个sRNA，其中251个为已知sRNA，另有50个为潜在新型sRNA。ASP组与HAM组间存在68个差异表达的已知sRNA。与ASP组相比，HAM组受试者体内有88个成熟微小RNA（microRNA, miRNA）表达下调。其中3个miRNA（hsa-miR-185-5p、hsa-miR-32-5p及hsa-miR-192-5p）具备作为预测HAM/TSP发病机制的生物标志物的潜力。这7个差异表达最为显著的miRNA的靶基因，参与了多种生物学过程与分子功能。与本研究结果相关的Reactome生物通路数据集内容丰富，为深入探究HTLV-1病理生理过程中的sRNA调控机制与功能提供了重要契机。据我们所知，本研究首次针对HTLV-1感染合并HAM/TSP的患者，对其体内sRNA进行了系统性分析与评估。