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MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma.
J Oral Pathol Med. 2018 Jan; 47(1):78-85.JO

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-miR-138-5p 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.

Authors+Show Affiliations

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.Department of Dentistry, Universidade Estadual de Montes Claros (UNIMONTES), Montes Claros, Brazil.Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.Stomatology Service, Odilon Behrens Hospital, Belo Horizonte, Brazil.Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.Centro de Pesquisas René Rachou (CPqRR), FIOCRUZ, Belo Horizonte, Brazil.Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29032608

Citation

Pereira, Thaís Dos Santos Fontes, et al. "MicroRNA Profiling Reveals Dysregulated microRNAs and Their Target Gene Regulatory Networks in Cemento-ossifying Fibroma." Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, vol. 47, no. 1, 2018, pp. 78-85.
Pereira TDSF, Brito JAR, Guimarães ALS, et al. MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma. J Oral Pathol Med. 2018;47(1):78-85.
Pereira, T. D. S. F., Brito, J. A. R., Guimarães, A. L. S., Gomes, C. C., de Lacerda, J. C. T., de Castro, W. H., Coimbra, R. S., Diniz, M. G., & Gomez, R. S. (2018). MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma. Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 47(1), 78-85. https://doi.org/10.1111/jop.12650
Pereira TDSF, et al. MicroRNA Profiling Reveals Dysregulated microRNAs and Their Target Gene Regulatory Networks in Cemento-ossifying Fibroma. J Oral Pathol Med. 2018;47(1):78-85. PubMed PMID: 29032608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma. AU - Pereira,Thaís Dos Santos Fontes, AU - Brito,João Artur Ricieri, AU - Guimarães,André Luiz Sena, AU - Gomes,Carolina Cavaliéri, AU - de Lacerda,Júlio Cesar Tanos, AU - de Castro,Wagner Henriques, AU - Coimbra,Roney Santos, AU - Diniz,Marina Gonçalves, AU - Gomez,Ricardo Santiago, Y1 - 2017/11/01/ PY - 2017/10/07/accepted PY - 2017/10/17/pubmed PY - 2018/9/5/medline PY - 2017/10/17/entrez KW - bone neoplasms KW - gene expression KW - microRNA KW - odontogenic tumour KW - ossifying fibroma SP - 78 EP - 85 JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JO - J Oral Pathol Med VL - 47 IS - 1 N2 - 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-miR-138-5p 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. SN - 1600-0714 UR - https://www.unboundmedicine.com/medline/citation/29032608/MicroRNA_profiling_reveals_dysregulated_microRNAs_and_their_target_gene_regulatory_networks_in_cemento_ossifying_fibroma_ DB - PRIME DP - Unbound Medicine ER -