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2035-01-01
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MICRORNA PROFILING REVEALS DYSREGULATED MICRORNAS AND THEIR TARGET GENE REGULATORY NETWORKS IN CEMENTO-OSSIFYING FIBROMA
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Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Estadual de Montes Claros. Departamento de Odontologia. Montes Claros, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas Departamento de Patologia. Belo Horizonte, MG, Brazil
Hospital Odilon Behrens. Serviço de estomatologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Insituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Estadual de Montes Claros. Departamento de Odontologia. Montes Claros, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas Departamento de Patologia. Belo Horizonte, MG, Brazil
Hospital Odilon Behrens. Serviço de estomatologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Insituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Odondologia. Departamento de Cirurgia Oral e Patologia. Belo Horizonte, MG, Brazil
Abstract
Background: Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis.
Methods: Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan OpenArray Human microRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath.
Results: Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR138-5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K-Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis.
Conclusion: miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation.
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