Background 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. Methods 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. Results 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. Conclusions 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.

中文翻译：

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非编码 RNome 的全球表达揭示了 HTLV-1 相关成人 T 细胞白血病患者中小 RNA 的失调：一项初步研究

背景成人 T 细胞淋巴瘤/白血病 (ATLL) 是由人类 T 细胞嗜淋巴细胞病毒 1 (HTLV-1) 引起的外周 T 细胞肿瘤。小 RNA (sRNA)，包括 microRNA (miRNA)，在血液系统恶性肿瘤的发生和发展中起关键作用，并且可能代表潜在的治疗靶分子。然而，人们对这些分子如何影响 ATLL 的发病机制知之甚少。在这项研究中，我们旨在鉴定与 ATLL 相关的 sRNA 表达特征，并研究它们在疾病病理生理学中的潜在影响。方法 与无症状携带者 (n = 8) 和健康对照 (n = 5) 相比，对来自 HTLV-1 相关 ATLL (n = 10) 的外周血单核细胞进行小 RNAseq 分析。使用 Illumina MiSeq 平台进行测序，并且通过实时 PCR 验证了所选 miRNA 的失调。对大多数失调的 miRNA 进行了通路分析，并将它们的全局分析与 ATLL 中的转录组数据相结合。结果测序鉴定了与 ATLL 患者相关的特定 sRNA 特征，这些特征靶向 ATLL 相关通路，例如转化生长因子 - (βTGF-β)、Wnt、p53、细胞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 在 ATLL 转录组内调节高度连接的基因。miR-451-3p 是活跃患者中下调幅度最大的 miRNA。结论我们的研究结果阐明了 HTLV-1 相关 ATLL 中特定 sRNA 的表达，这可能代表作为帮助监测疾病活动的生物标志物的有希望的候选者。