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Posttranscriptional Repression of FBXW7 and FBXO8 by microRNA-223 Regulates Ubiquitin-dependent Proteostasis in Periodontal Disease

Contemp Clin Dent. 2026 Jan-Mar;17(1):39-47. doi: 10.4103/ccd.ccd_486_25. Epub 2026 Mar 26.

ABSTRACT

BACKGROUND: The microRNA-223 (miR-223)/FBXW7/FBXO8 molecular network governs ubiquitin-proteasome proteostasis, a cardinal process in cellular protein turnover. Dysregulation amplifies inflammatory cascades and expedites tissue degradation. This study elucidates stage-specific expression divergences of miRNAs-223 and its cognate F-box regulators in periodontitis.

MATERIALS AND METHODS: This observational study enrolled 100 participants, categorized into five groups comprising periodontally healthy individuals and patients with Stage I-IV Grade B periodontitis. Gingival crevicular fluid (GCF) was collected using calibrated microcapillary pipettes. Total RNA was isolated from the GCF specimens, followed by complementary DNA (cDNA) conversion. Expression levels of miRNAs-223, FBXW7, and FBXO8 across all groups were assessed through the real-time quantitative PCR methodology. In silico target prediction analyses for miRNAs-223 and functional enrichment analyses were performed using the bioinformatic tools.

RESULTS: Expression analysis of GCF across Groups A (Healthy) to E (Stage IV) revealed statistically significant upregulation of miR-223 (25.38 ± 2.56; P = 0.001), accompanied by marked downregulation of FBXW7 (0.02 ± 2.05; P = 0.001) and FBXO8 (0.11 ± 2.04; P = 0.02). miR-223 levels positively correlated with clinical parameters, while FBXW7 and FBXO8 showed inverse correlations, strengthening with disease severity. Notably, miR-223 exhibited significant negative associations with both F-box proteins. Receiver operating characteristic analysis confirmed its diagnostic utility (AUC 0.919), highlighting miR-223 as a potential molecular signature for periodontal disease.

CONCLUSION: The pathophysiological derangement of the miR-223/FBXO8/FBXW7 signaling axis is entwined with aberrant proteolytic dynamics in periodontal pathology, accentuating the indispensable role of F-box-dependent ubiquitin-mediated degradation and positioning this molecular ensemble as a promising conduit for therapeutic stratagem.

PMID:41953918 | PMC:PMC13056218 | DOI:10.4103/ccd.ccd_486_25

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