microRNAs regulate the pathogenesis of gingival overgrowth.
Date Issued
2009
Date
2009
Author(s)
Kao, Pei-Chi
Abstract
The increase of size in gingiva, named gingival overgrowth or gingival enlargement, is a common feature of gingival disease. Risk of recurrence in the patients with idiopathic or drug-induced gingival overgrowth is really a challenge to a periodontist. And the overgrowth lesions are characterized by epithelial acanthosis, with long, branched rete peg formation, and the excessive accumulation of radiating collagen fibers in the connective tissue layer. But the etiology and pathogenic mechanism of gingival overgrowth are still unclear. microRNAs (miRNAs) are a family of small non-coding RNA molecules of about 22 nucleotides in length, which involved in post-transcriptional gene regulation and regulated development, proliferation, apoptosis…etc. miRNAs control the expression of target genes by inhibiting translation or degradating target mRNAs through binding to their 3’UTR. The present study demonstrated the gingival overgrowth is characterized by specific miRNAs expression profile. In the preliminary study, we established a databank by using microarray analysis of miRNAs and gene expression from one patient with inherited gingival fibromatosis. Now, we expanded the sample size to three to decrease the interference of individual predisposition, and we successfully identified 6 specific miRNAs with consistent expression tendency in the overgrowth gingival tissues, including miR-203, -143, -145, -200a, -200b, -923. Furthermore, we used real time RT-PCR to verify the microarray data. Considering about the expression predominance of miRNAs in different cell types, we separated the gingiva to epithelial and connective tissue layers. We quantified the exression levels of 6 miRNAs in 9 patients (5 patients in experimental group; 4 patients in control group) after informed consent. miR-203, -143, -145, -200a, -200b in the epithelial layer and miR-143, -145 in the connective tissue layer are significantly downregulated in gingival overgrowth samples. The putative target of miR-203 is p63, whose mRNA and protein level expression are significantly increased. Therefore we postulate that miR-203 involves the biological function by regulating p63. The downregulation of anti-oncomir, miR-143 and miR-145, drives the increasing of cell number, which corresponds to the clinical and pathological features of gingival overgrowth. miR-200 family regulates the epithelial-mesenchymal transition (EMT) by targeting ZEB1 and SIP1. In our study, miR-200 family downregulated, TGF-β upregulated, E-cadherin decreased, SIP1 increased, and cell morphology changed, which were similar to EMT process. Although we need more future studies to clarify the exact biological function of miRNAs, we still explore a new direction to interpret the pathogenesis of gingival overgrowth.
Subjects
gingival overgrowth
miRNA
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