NCK1 antisense RNA 1 (NCK1-AS1) exerts pro-fibrosis property in oral mucosa through modulation of miR-137/NCK1 axis.

Background/purpose: Oral submucous fibrosis (OSF) is a premalignant condition of the oral cavity, and its pathogenesis remains largely unknown. A multitude of non-coding RNAs are aberrantly expressed in OSF, and their implication for the development of OSF is a matter meriting investigation.

Materials and methods: The functional role of long non-coding RNA NCK1-AS1 in myofibroblast activation of fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues was assessed. Wound healing, collagen gel contraction and transwell migration assays have been employed to assess the myofibroblast activities. In addition, a luciferase-based reporter assay was used to illustrate the potential mechanism underlying the regulation of NCK1-AS1 in myofibroblast activation.

Results: Silencing of NCK1-AS1 markedly downregulated myofibroblast activation and the expression of fibrosis markers in fBMFs. Besides, we demonstrated that NCK1-AS1 directly interacted with microRNA-137 (miR-137) and was negatively correlated with it. Moreover, we found that NCK1 was a target of miR-137 and positively related to NCK1-AS1. Our results demonstrated that NCK1-AS1 may regulate myofibroblast activation by suppressing miR-137 and upregulating NCK1.

Conclusion: We showed that NCK1-AS1 acted as a sponge of miR-137 and titrated the suppressive effect of miR-137 on NCK1 to modulate myofibroblast activation in OSF condition.