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

• Published in: Infectious agents and cancer Vol. 16; no. 1; p. 4
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.01.2021; BioMed Central; BMC
• Subjects: Analysis; Apoptosis; Asymptomatic; Asymptomatic carriers; Blood & organ donations; Cancer; Care and treatment; Deoxyribonucleic acid; DNA; DNA methylation; Epigenetics; Gene expression; Genetic research; Health aspects; HTLV-1; Infections; Leukemia; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; MAP kinase; Massively parallel sequencing; MicroRNA; MicroRNAs; miRNA; Mitogens; Neoplasia; Oncology, Experimental; p53 Protein; Pathogenesis; Pathophysiology; Peripheral blood mononuclear cells; Protein kinase; Protein kinases; Proteins; RNA polymerase; RNA sequencing; Small RNA; T cell antigen receptor; T cell receptors; T cells; T-cell lymphoma; Therapeutic targets; Transcriptomes; Transfer RNA; Transforming growth factors; Tumor proteins; Viral infections; Viruses; Wnt protein; Japan; Germany; Massively parallel sequencing; HTLV-1; Asymptomatic carriers; Small RNA; T cell antigen receptor
• ISSN: 1750-9378; 1750-9378
• 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.