Inhibition of HIF1A-AS1 impedes the arecoline-induced migration activity of human oral mucosal fibroblasts

Long non-coding RNA hypoxia-inducible factor 1α-antisense RNA 1 (HIF1A-AS1) has been known to participate in various types of malignancies, but its role in the development of precancerous oral submucous fibrosis (OSF) has not been investigated. In the current study, we first observed the aberrant upregulation of HIF1A-AS1 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) isolated from OSF specimens. Next, we demonstrated that administration of arecoline, a natural alkaloid that is found in areca nut, induced the elevation of HIF1A-AS1 in BMFs. This finding showed that the habit of areca nut chewing may lead to an increase of HIF1A-AS1 in oral mucosa. Moreover, we found that knockdown of HIF1A-AS1 hindered the arecoline-stimulated migration capacity in BMFs, suggesting HIF1A-AS1 was critical to the transdifferentiation of BMFs into myofibroblasts. Altogether, our results demonstrated that overexpression of HIF1A-AS1 in OSF tissues may result from the use of areca nut and lead to activation of BMFs, which contribute to the progression of OSF.