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MicroRNA global expression profile in patients with Intestinal Neuronal Dysplasia type B

Grant number: 15/03664-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine - Surgery
Principal researcher:Pedro Luiz Toledo de Arruda Lourencao
Grantee:Alana Maia e Silva
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Intestinal Neuronal Dysplasia Type B (INDB) is a gastrointestinal neuromuscular disease, characterized by complex changes in the enteric nervous system. Despite recent advances in the study of this disease, there are still some uncertainties regarding to its definition, diagnostic criteria and therapeutic possibilities, which makes the elucidation of its pathogenesis and pathophysiology as the main goal of scientific research. INDB possibly originates from a primary genetically change, which directly influences embryological development of tissues derived from the neural crest. Recent studies have investigated the role of genetic and molecular controls on the migration and development of cells of the enteric nervous system. Different studies in animals have shown that some mutations may determine megacolon and hyperplasia of the myenteric nervous plexus. However, these same results were not found in patients with INDB. MicroRNAs (miRNAs) are small RNAs of about 19 to 25 nucleotides in length, not protein-coding but which act in the regulation of a large proportion of genes in the human genome. The advances in the discovery of miRNAs as regulators of the gene expression and its role in different pathologies suggest that these molecules represent strong biomarkers for the diagnosis, the prognosis and as potential new therapeutic targets in human diseases. Thus, the evaluation of the expression of miRNAs in peripheral blood and in rectal biopsy samples from patients with INDB can provide valuable information to elucidate the pathogenesis and pathophysiology of this disease, representing a key step for further progress related to its diagnosis and treatment. Objective: Determine the miRNA global expression profile in peripheral blood and in rectal biopsy samples from patients with INDB. Methods: 63 INDB patients, aged 0-15 years, will be analyzed. The patients will be asked to collect a blood sample (5ml) for RNA extraction and expression analysis of circulating miRNAs. In a second step, the paraffin blocks of the rectal biopsies of these patients will be recovered to collect tissue samples for molecular expression analysis of miRNAs. The global analysis of miRNA expression is performed by TaqMan ® Human MicroRNA Array Card The v2.0 platform, which consists of a lyophilized probe card, which enables precise quantification of 374 human miRNAs. Data analysis is performed using the RQ Manager v1.2 program (Life Technologies). Statistical algorithms using One-Way ANOVA and hierarchical clustering will be applied in order to identify which miRNAs have significantly dysregulated expression in biopsy samples and peripheral blood of patients with INDB.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANGELINI, MARCOS C.; SILVA, ALANA MAIA E.; FELIX, TAINARA F.; LAPA, RAINER M. L.; TERRA, SIMONE A.; RODRIGUES, MARIA A. M.; ORTOLAN, ERIKA V. P.; REIS, PATRICIA P.; LOURENCAO, PEDRO L. T. A.. Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B. SCIENTIFIC REPORTS, v. 9, . (14/04271-1, 15/03664-2, 14/00367-4)

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