miR‐200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting <scp>ZEB</scp>2

<jats:title>Abstract</jats:title><jats:p>Oral submucous fibrosis (<jats:styled-content style="fixed-case">OSF</jats:styled-content>) is a progressive scarring disease. Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐200b (miR‐200b) has been reported as a tumour suppressor, but its role in the precancerous <jats:styled-content style="fixed-case">OSF</jats:styled-content> remains unknown. In this study, we investigated the impact of miR‐200b on myofibroblastic differentiation activity. Arecoline is a major areca nut alkaloid and has been employed to induce the elevated myofibroblast activity in human buccal mucosal fibroblasts (<jats:styled-content style="fixed-case">BMF</jats:styled-content>s). Treatment of arecoline in <jats:styled-content style="fixed-case">BMF</jats:styled-content>s dose‐dependently reduced gene expression of miR‐200b, which corresponded with the decreased expression of miR‐200b in <jats:styled-content style="fixed-case">fBMF</jats:styled-content>s. The arecoline‐induced myofibroblast activities were abolished by overexpression of miR‐200b in <jats:styled-content style="fixed-case">BMF</jats:styled-content>s, and the same results were observed in <jats:styled-content style="fixed-case">fBMF</jats:styled-content>s. In addition, α‐<jats:styled-content style="fixed-case">SMA</jats:styled-content> was inhibited by an increase in miR‐200b. We further demonstrated that miR‐200b‐mediated decrease in <jats:styled-content style="fixed-case">ZEB</jats:styled-content>2 led to down‐regulation of α‐<jats:styled-content style="fixed-case">SMA</jats:styled-content>, vimentin. Loss of miR‐200b resulted in enhanced collagen contraction and migration capabilities, and knockdown of <jats:styled-content style="fixed-case">ZEB</jats:styled-content>2 reversed these phenomena. Lastly, we showed the expression of miR‐200b was significantly less and <jats:styled-content style="fixed-case">ZEB</jats:styled-content>2 was markedly higher in <jats:styled-content style="fixed-case">OSF</jats:styled-content> tissues. These results suggested that down‐regulation of miR‐200b may contribute to the pathogenesis of areca quid‐associated <jats:styled-content style="fixed-case">OSF</jats:styled-content> through the regulation of <jats:styled-content style="fixed-case">ZEB</jats:styled-content>2 and myofibroblast hallmarks.</jats:p>