Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B

Autor(es)

Angelini, Marcos C. ^[1] ; Silva, Alana Maia E. ^[1] ; Felix, Tainara F. ^{[1, 2]} ; Lapa, Rainer M. L. ^[3] ; Terra, Simone A. ^[4] ; Rodrigues, Maria A. M. ^[4] ; Ortolan, Erika V. P. ^[1] ; Reis, Patricia P. ^{[1, 2]} ; Lourencao, Pedro L. T. A. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Sao Paulo State Univ, Fac Med, Dept Surg & Orthoped, Botucatu, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Fac Med, Expt Res Unity UNIPEX, Botucatu, SP - Brazil

^[3] Toribio Rodriguez de Mendoza Natl Univ, Lab Mol Physiol, Inst Livestock & Biotechnol, Amazonas - Peru

^[4] UNESP Sao Paulo State Univ, Fac Med, Dept Pathol, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, NOV 27 2019.
• Citações Web of Science: 0

Resumo

This study proposed to determine global microRNA (miRNA) expression and miRNA-regulated pathways in Intestinal Neuronal Dysplasia type B (IND-B). Fifty patients (0-15 years old) with IND-B were included in the study. Peripheral blood samples were collected from all 50 patients and from 10 healthy asymptomatic children (controls). Rectal biopsies were collected from 29/50 patients; biopsy tissues were needle microdissected to isolate the different intestinal layers, for molecular analysis. Global miRNA expression was determined using TaqMan arrays. Correlation analysis between miRNA expression in plasma and biopsy samples as well as among tissues derived from the distinct intestinal layers was performed. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated genes and enriched pathways biologically relevant to IND-B pathogenesis. miRNAs were statistically significantly deregulated (FC >= 2 and p <= 0.05) in submucosal and muscular layers: over-expressed (miR-146a and miR-146b) and under-expressed (miR-99a, miR-100, miR-130a, miR-133b, miR-145, miR-365, miR-374-5p, miR-451). Notably, let-7a-5p was highly over-expressed in patient plasma compared to healthy controls (FC = 17.4). In addition, miR-451 was significantly under-expressed in both plasma and all biopsy tissues from the same patients. Enriched pathways (p < 0.01) were axon guidance, nerve growth factor signalling, NCAM signalling for neurite out-growth, neuronal system and apoptosis. miRNA expression is deregulated in the submucosa and muscular layers of the rectum and detected in plasma from patients with IND-B. Biologically enriched pathways regulated by the identified miRNAs may play a role in IND-B disease pathogenesis, due to the activity related to the neurons of the enteric nervous system. (AU)

• Processo FAPESP: 14/04271-1 - Evolução clínica de pacientes com displasia neuronal intestinal: qual é o melhor tratamento?
• Beneficiário: Pedro Luiz Toledo de Arruda Lourencao
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/03664-2 - Determinação do perfil molecular de microRNAs em Displasia Neuronal Intestinal Tipo B
• Beneficiário: Alana Maia e Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/00367-4 - MicroRNoma do carcinoma de pâncreas
• Beneficiário: Tainara Francini Felix
• Modalidade de apoio: Bolsas no Brasil - Mestrado