MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento‐ossifying fibroma

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Excerpt

Cemento‐ossifying fibroma (COF) is a benign fibro‐osseous well‐delimited neoplasm, consisting of mineralised deposits, permeated by fibrocellular tissue.1 Clinically, COF presents as an expansive and often painless enlargement, which mainly affects the posterior region of the jaw, occasionally causing tooth displacement.2 The diagnosis of a benign fibro‐osseous lesion requires the evaluation of clinical, radiographic, histopathological and transoperative findings, such as the relation of the lesion to healthy surrounding bone.4 Conservative surgery is the first choice of treatment, and, as the tumour may reach large dimensions, morbidity is often experienced after excision.3 The recurrence rate can vary from 12% to 28%.5
Regarding the molecular characterisation of COF pathogenesis, there are few elucidative studies. Mutations in the CDC73 (HRPT2) tumour suppressor gene have been described in the hyperparathyroidism‐jaw tumour syndrome‐HPTJT,7 and about 40% of HPTJT individuals develop COF in the jaws.8 Missense mutations in CDC73 were also reported in sporadic COF,9 but it does not seem to have a central role in COF pathogenesis.10 Genetic alterations in CTNNB1 and APC were identified by Horvai & Jordan11 in two cases of conventional COF. However, there is no evidence of the role of these variants in the pathogenesis of the lesion. As genomic alterations have not yet been described as driver events to COF development, the search for epigenetic mechanisms may shed light on COF pathogenesis.
miRNAs are small non‐coding RNA molecules that regulate gene expression post‐transcriptionally by binding to the 3′ UTR of target mRNAs.12 They have been the subject of studies that aimed at the identification of potential biomarkers and prognostic indicators of bone neoplasms. For example, metastatic osteosarcoma shows upregulation of miR‐27a and miR‐181c.13 Also, overexpression of miR‐199a‐5p was reported in plasma from patients with osteosarcoma compared to controls.14 miRNAs are also important modulators in cell differentiation process. Increased expression of miR‐142‐3p,15 miR‐2716 and miR‐ 26a was found during osteoblastic differentiation. Regulation by miRNAs has been described as an important mechanism in the pathogenesis of several disorders, and, as their function can be manipulated through antisense oligonucleotides, they represent a potential therapeutic tool.17 To date, miRNAs expression profile in benign fibro‐osseous lesions such as COF is unknown. The purpose of this study was to compare 754 miRNAs expression in conventional COF with normal bone and investigate the most relevant potential pathways and target genes of dysregulated miRNA through bioinformatics tools.
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