Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

Abstract

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 on 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 TGF-β, Wnt, p53, apoptosis, and 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.

Small RNA Profiling in HTLV-1-infected Patient with Acute Adult T-cell Leukemia-Lymphoma at Diagnosis and After Maintenance Therapy: A Case Study

“…To date, HTLV-I-infected cell lines have been studied using microarray and PCR-based approaches to identify and characterize cellular miRNAs [18]. Our group recently revealed distinct sRNA signatures for ATLL and proposed that these signatures could be employed as biomarkers to detect ATLL at an early stage [19]. Furthermore, in patients with active ATLL, we observed that miR-451-3p was the miRNA that was most significantly downregulated, suggesting that this miR could be a promising therapeutic target in ATLL via the AMPK/Notch signaling pathway.…”