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

Autor(es):Mostrar menos -

Nascimento, Andrezza ^[1] ; Valadao de Souza, Daniela Raguer ^[1] ; Pessoa, Rodrigo ^[1] ; Pietrobon, Anna Julia ^[1] ; Nukui, Youko ^[2] ; Pereira, Juliana ^[2] ; Casseb, Jorge ^[1] ; Penalva de Oliveira, Augusto Cesar ^[3] ; Loureiro, Paula ^[4] ; da Silva Duarte, Alberto Jose ^[1] ; Clissa, Patricia Bianca ^[5] ; Sanabani, Sabri Saeed ^[6]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Med Trop Sao Paulo, Fac Med, Dept Dermatol, Lab Dermatol & Immunodeficiency, Av Dr Eneas de Carvalho Aguiar 470, 3 Andar, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Hematol, BR-05403000 Sao Paulo - Brazil

^[3] Emilio Ribas Inst Infectol, Dept Neurol, BR-01246900 Sao Paulo - Brazil

^[4] Pernambuco State Ctr Hematol & Hemotherapy, BR-52011900 Recife, PE - Brazil

^[5] Butantan Inst, Immunopathol Lab, BR-05503900 Sao Paulo - Brazil

^[6] Univ Sao Paulo, Clin Hosp, Fac Med, Lab Med Invest, Unit 03, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INFECTIOUS AGENTS AND CANCER; v. 16, n. 1 DEC 9 2021.
• Citações Web of Science: 0

Resumo

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-(beta TGF-beta), 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. (AU)

• Processo FAPESP: 18/08631-3 - Composição e diversidade da comunidade bacteriana no reservatório de Billings através do sequenciamento de nova geração do gene 16S rRNA
• Beneficiário: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Modalidade de apoio: Auxílio à Pesquisa - Regular