Postgraduate Program in Translational Medicine, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Department of Hematology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Virulence. 2023 Dec;14(1):2230015. doi: 10.1080/21505594.2023.2230015.
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 ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 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(HTLV-1)相关脊髓病/热带痉挛性截瘫(HAM/TSP)是一种进行性进展的脊髓疾病,目前尚无有效的治疗方法。人们非常有兴趣开发潜在的生物标志物来预测 HAM/TSP 疾病的发病机制。在这项研究中,使用 Illumina 大规模平行测序(MPS)技术研究了 HAM/TSP 患者(n=10)、无症状 HTLV-1 感染携带者(ASP,n=8)和第二组健康对照组(n=5)的细胞全局非编码 RNAome 表达谱。使用各种生物信息学工具来对齐、注释和分析 sRNA-MPS 读段。在检测到的 402 个 sRNA 中,与 HC 组相比,HAM 和 ASP 组中有 251 个是已知的,50 个是潜在的新 sRNA。在 ASP 和 HAM 组之间有 68 个已知的 sRNA 存在显著差异。与 ASP 相比,来自 HAM 的受试者中有 88 个成熟的 miRNA 下调。其中三个 miRs(hsa-miR-185-5p、32-5p 和 192-5p)具有作为预测 HAM/TSP 发病机制的生物标志物的潜力。七个最失调的 miRs 的靶基因与多种生物学过程和分子功能相关。与我们的发现相关的反应途径提供了丰富的数据来源,并为更好地理解 sRNA 在 HTLV-1 病理生理学中的调节和功能提供了机会。据我们所知,这项研究首次评估了 HAM/TSP 患者的 sRNA。