Mechanism study of circCCDC134 regulating the biological behaviors of PDGF-BB-induced oral mucosal fibroblast.

The transition of fibroblasts into myofibroblasts is a key factor in oral submucous fibrosis (OSF) pathogenesis. Our previous studies demonstrated that platelet-derived growth factor-BB (PDGF-BB) promotes the proliferation, migration, and transition of human oral mucosal fibroblasts (HOMF) by downregulating microRNA-503 (miR-503). However, the mechanism underlying PDGF-BB-mediated miR-503 downregulation remained unclear. We identified eight exon-derived circRNA with m6A modification sites, moderate length, and strong predicted binding affinity for miR-503. Among these candidates, circCCDC134 exhibited the most significant upregulation in PDGF-BB-stimulated HOMF. Our functional studies revealed that circCCDC134 overexpression enhanced proliferation, migration, and transition of PDGF-BB-induced HOMF, whereas circCCDC134 silencing attenuated these effects. Mechanistically, PDGF-BB upregulates circCCDC134 expression in HOMF. Subsequently, circCCDC134 acts as a molecular sponge for miR-503, sequestering miR-503 and thereby relieving its repression of RAF mRNA. This leads to increased RAF protein expression, activation of the RAF/MEK/ERK signaling pathway, and ultimately promotes HOMF proliferation, migration, and transition. These findings establish a theoretical foundation for identifying potential biomarkers and therapeutic targets for the targeted treatment of OSF.