Ethyl 1,2,5,6-tetrahydropyridine-3-carboxylate

Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M.[Pubmed:29385191]

PLoS One. 2018 Jan 31;13(1):e0192009.

Arecoline, the major alkaloid of areca nut, is known to induce oral carcinogenesis, however, its mechanism is still needed to elucidate. This study investigated the effects of arecoline on cell viability and cell-cycle progression of oral squamous cell carcinoma (OSCC) cells as well as a relevant cellular gene expression. The results showed that a low concentration of arecoline (0.025 mug/ml) increased OSCC cell viability, proportion of cells in G2/M phase and cell proliferation. Simultaneously, it induced IL-6, STAT3 and c-Myc expression. Interestingly, c-myc promoter activity was also induced by arecoline. MiR-22 expression in arecoline-treated OSCC cells was suppressed and comparable to an upregulated c-Myc expression. In arecoline-treated OSCC cells, oncostatin M (OSM) expression was significantly upregulated and inversely correlated with miR-22 expression. Likewise, OSM expression and its post-transcriptional activity were significantly decreased in miR-22-transfected OSCC and 293FT cells. This result demonstrated that miR-22 directly targeted OSM. Interestingly, miR-22 played an important role as a tumor suppresser on suppressing cell proliferation, migration and cell-cycle progression of OSCC cells. This result suggested the effect of arecoline to promote cell proliferation and cell-cycle progression of OSCC cells might be involved in induction of c-Myc expression and reduction of miR-22 resulting in OSM upregulation.

miR-200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting ZEB2.[Pubmed:29893466]

J Cell Mol Med. 2018 Sep;22(9):4130-4138.

Oral submucous fibrosis (OSF) is a progressive scarring disease. MicroRNA-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 (BMFs). Treatment of arecoline in BMFs dose-dependently reduced gene expression of miR-200b, which corresponded with the decreased expression of miR-200b in fBMFs. The arecoline-induced myofibroblast activities were abolished by overexpression of miR-200b in BMFs, and the same results were observed in fBMFs. In addition, alpha-SMA was inhibited by an increase in miR-200b. We further demonstrated that miR-200b-mediated decrease in ZEB2 led to down-regulation of alpha-SMA, vimentin. Loss of miR-200b resulted in enhanced collagen contraction and migration capabilities, and knockdown of ZEB2 reversed these phenomena. Lastly, we showed the expression of miR-200b was significantly less and ZEB2 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 ZEB2 and myofibroblast hallmarks.