Open AccessmiR‐200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting ZEB 2
Author(s) -
Liao YiWen,
Yu ChengChia,
Hsieh PeiLing,
Chang YuChao
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13690
Subject(s) - arecoline , myofibroblast , oral submucous fibrosis , areca , vimentin , cancer research , gene knockdown , pathogenesis , fibrosis , microrna , downregulation and upregulation , transdifferentiation , pathology , medicine , biology , chemistry , microbiology and biotechnology , gene , immunohistochemistry , biochemistry , stem cell , receptor , structural engineering , nut , engineering , muscarinic acetylcholine receptor
Abstract Oral submucous fibrosis ( OSF ) is a progressive scarring disease. Micro RNA ‐200b (miR‐200b) has been reported as a tumour suppressor, but its role in the precancerous OSF 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 ( BMF s). Treatment of arecoline in BMF s dose‐dependently reduced gene expression of miR‐200b, which corresponded with the decreased expression of miR‐200b in fBMF s. The arecoline‐induced myofibroblast activities were abolished by overexpression of miR‐200b in BMF s, and the same results were observed in fBMF s. In addition, α‐ SMA was inhibited by an increase in miR‐200b. We further demonstrated that miR‐200b‐mediated decrease in ZEB 2 led to down‐regulation of α‐ SMA , vimentin. Loss of miR‐200b resulted in enhanced collagen contraction and migration capabilities, and knockdown of ZEB 2 reversed these phenomena. Lastly, we showed the expression of miR‐200b was significantly less and ZEB 2 was markedly higher in OSF tissues. These results suggested that down‐regulation of miR‐200b may contribute to the pathogenesis of areca quid‐associated OSF through the regulation of ZEB 2 and myofibroblast hallmarks.