Andrezza Nascimento1, Daniela Raguer Valadão de Souza1, Rodrigo Pessôa1, Anna Julia Pietrobon1, Youko Nukui2, Juliana Pereira2, Jorge Casseb1, Augusto César Penalva de Oliveira3, Paula Loureiro4, Alberto José da Silva Duarte1, Patricia Bianca Clissa5, Sabri Saeed Sanabani6. 1. 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. 2. Department of Hematology, Faculty of Medicine, University of São Paulo, São Paulo, 05403 000, Brazil. 3. Department of Neurology, Emilio Ribas Institute of Infectious Diseases, São Paulo, 01246-900, Brazil. 4. Pernambuco State Center of Hematology and Hemotherapy, Recife, Pernambuco, CEP 52011900, Brazil. 5. Immunopathology Laboratory, Butantan Institute, São Paulo, 05503-900, Brazil. 6. Laboratory of Medical Investigation Unit 03, Clinics Hospital, Faculty of Medicine, University of São Paulo, São Paulo, 05403 000, Brazil. sabyem_63@yahoo.com.
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 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.
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 ATLLpatients 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.
Entities:
Keywords:
Asymptomatic carriers; HTLV-1; Massively parallel sequencing; Small RNA; T cell antigen receptor
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