Nascimento Andrezza, Valadão de Souza Daniela Raguer, Pessôa Rodrigo, Pietrobon Anna Julia, Nukui Youko, Pereira Juliana, Casseb Jorge, Penalva de Oliveira Augusto César, Loureiro Paula, da Silva Duarte Alberto José, Clissa Patricia Bianca, Sanabani Sabri Saeed
Laboratory of Dermatology and Immunodeficiency, Department of Dermatology, Instituto de Medicina Tropical de São Paulo, Faculty of Medicine, University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 470 3° andar, São Paulo, 05403 000, Brazil.
Department of Hematology, Faculty of Medicine, University of São Paulo, São Paulo, 05403 000, Brazil.
Infect Agent Cancer. 2021 Jan 9;16(1):4. doi: 10.1186/s13027-020-00343-2.
Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease.
Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL.
The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients.
Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.
成人T细胞淋巴瘤/白血病（ATLL）是一种由人类T细胞嗜淋巴细胞病毒1型（HTLV-1）引起的外周T细胞肿瘤。包括微小RNA（miRNA）在内的小RNA（sRNA）在血液系统恶性肿瘤的发生和发展中起关键作用，可能代表潜在的治疗靶点分子。然而，关于这些分子如何影响ATLL的发病机制知之甚少。在本研究中，我们旨在鉴定与ATLL相关的sRNA表达特征，并研究它们在该疾病病理生理学中的潜在意义。
对来自HTLV-1相关ATLL患者（n = 10）、无症状携带者（n = 8）和健康对照（n = 5）的外周血单个核细胞进行小RNA测序分析。使用Illumina MiSeq平台进行测序，并通过实时PCR验证所选miRNA的失调情况。对失调最明显的miRNA进行通路分析，并将其整体谱与ATLL中的转录组数据相结合。
测序鉴定出与ATLL患者相关的特定sRNA特征，这些特征靶向ATLL中相关的通路，如转化生长因子-β（TGF-β）、Wnt、p53、凋亡和丝裂原活化蛋白激酶（MAPK）信号级联。网络分析揭示了几种miRNA调节ATLL转录组内高度连接的基因。miR-451-3p是活动期患者中下调最明显的miRNA。
我们的研究结果揭示了HTLV-1相关ATLL中特定sRNA的表达情况，这些sRNA可能是有前景的生物标志物候选物，有助于监测疾病活动。
