Curcumin suppresses EMT to alleviate oral submucous fibrosis progression through XIST/miR-25-3p-mediated inactivation of the TGF-β1/Smads signalling pathway.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic oral disease with a tendency to carcinogenesis. At present, the treatment of OSF is limited and ineffective, and there is an urgent need to find new effective drugs and mechanisms of action.

METHODS: Arecoline was used to induce human oral mucosal fibroblasts (HOFs) to establish OSF cell model. The effects of curcumin on the proliferation, migration and invasion of HOFs were detected by CCK-8 and Transwell. Western blot (WB) was used to detect the effect of curcumin on epithelial-mesenchymal transition (EMT) process and TGF-β1/Smads signalling pathway. The regulation of XIST and miR-25-3p expression by curcumin was detected by qRT-PCR, and the role of XIST/miR-25-3p axis in curcumin function was investigated by rescue assay to detect cell viability, EMT progression and TGF-β1/Smads signalling pathway.

RESULTS: Curcumin significantly inhibited HOF cell viability (about 58%) and EMT process, down-regulate the expression of mesenchymal markers N-cadherin and Vimentin (over 40%), up-regulate the expression of epithelial marker E-cadherin (twice), and inhibit the activation of TGF-β1/Smads signalling pathway (about 50%). Curcumin regulated the expression levels of XIST (downregulated by approximately 58%) and miR-25-3p (increased by more than twice), and XIST regulated the expression of miR-25-3p through sponge adsorption. Further studies confirmed that curcumin regulated HOF cell activity, EMT process and TGF-β1/Smads signalling pathway through the XIST/miR-25-3p axis.

CONCLUSIONS: Curcumin effectively inhibits EMT by inactivating the TGF-β1/Smads pathway through regulating XIST/miR-25-3p, and thereby alleviating the progression ofOSF. The study results further reveal the mechanisms underlying the function of curcumin, and may provide novel targets and ideas for OSF therapy.