Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-019-54245-4 http://hdl.handle.net/11449/199725 |
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. |
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Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type BThis 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)UNESP - São Paulo State University Faculty of Medicine Department of Surgery and OrthopedicsUNESP - São Paulo State University Faculty of Medicine Experimental Research Unity (UNIPEX)Institute of Livestock and Biotechnology Laboratory of Molecular Physiology Toribio Rodriguez de Mendoza National UniversityUNESP - São Paulo State University Faculty of Medicine Department of PathologyUNESP - São Paulo State University Faculty of Medicine Department of Surgery and OrthopedicsUNESP - São Paulo State University Faculty of Medicine Experimental Research Unity (UNIPEX)UNESP - São Paulo State University Faculty of Medicine Department of PathologyFAPESP: 2015/03664-2Universidade Estadual Paulista (Unesp)Toribio Rodriguez de Mendoza National UniversityAngelini, Marcos C. [UNESP]Silva, Alana Maia e. [UNESP]Felix, Tainara F. [UNESP]Lapa, Rainer M. L.Terra, Simone A. [UNESP]Rodrigues, Maria A. M. [UNESP]Ortolan, Erika V. P. [UNESP]Reis, Patricia P. [UNESP]Lourenção, Pedro L. T. A. [UNESP]2020-12-12T01:47:38Z2020-12-12T01:47:38Z2019-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-54245-4Scientific Reports, v. 9, n. 1, 2019.2045-2322http://hdl.handle.net/11449/19972510.1038/s41598-019-54245-42-s2.0-85075677600Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reportsinfo:eu-repo/semantics/openAccess2021-10-23T09:13:51Zoai:repositorio.unesp.br:11449/199725Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T09:13:51Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
title |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
spellingShingle |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B Angelini, Marcos C. [UNESP] |
title_short |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
title_full |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
title_fullStr |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
title_full_unstemmed |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
title_sort |
Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B |
author |
Angelini, Marcos C. [UNESP] |
author_facet |
Angelini, Marcos C. [UNESP] Silva, Alana Maia e. [UNESP] Felix, Tainara F. [UNESP] Lapa, Rainer M. L. Terra, Simone A. [UNESP] Rodrigues, Maria A. M. [UNESP] Ortolan, Erika V. P. [UNESP] Reis, Patricia P. [UNESP] Lourenção, Pedro L. T. A. [UNESP] |
author_role |
author |
author2 |
Silva, Alana Maia e. [UNESP] Felix, Tainara F. [UNESP] Lapa, Rainer M. L. Terra, Simone A. [UNESP] Rodrigues, Maria A. M. [UNESP] Ortolan, Erika V. P. [UNESP] Reis, Patricia P. [UNESP] Lourenção, Pedro L. T. A. [UNESP] |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Toribio Rodriguez de Mendoza National University |
dc.contributor.author.fl_str_mv |
Angelini, Marcos C. [UNESP] Silva, Alana Maia e. [UNESP] Felix, Tainara F. [UNESP] Lapa, Rainer M. L. Terra, Simone A. [UNESP] Rodrigues, Maria A. M. [UNESP] Ortolan, Erika V. P. [UNESP] Reis, Patricia P. [UNESP] Lourenção, Pedro L. T. A. [UNESP] |
description |
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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-01 2020-12-12T01:47:38Z 2020-12-12T01:47:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41598-019-54245-4 Scientific Reports, v. 9, n. 1, 2019. 2045-2322 http://hdl.handle.net/11449/199725 10.1038/s41598-019-54245-4 2-s2.0-85075677600 |
url |
http://dx.doi.org/10.1038/s41598-019-54245-4 http://hdl.handle.net/11449/199725 |
identifier_str_mv |
Scientific Reports, v. 9, n. 1, 2019. 2045-2322 10.1038/s41598-019-54245-4 2-s2.0-85075677600 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799964994761129984 |