LncRNA GAS5-AS1 inhibits myofibroblasts activities in oral submucous fibrosis

J Formos Med Assoc. 2018 Aug;117(8):727-733. doi: 10.1016/j.jfma.2017.09.012. Epub 2017 Dec 15.

Abstract

Background/purpose: Emerging research findings suggest that long non-coding RNAs (lncRNAs) are key regulators to fibrosis formation. Nevertheless, the role of lncRNA GAS5-AS1 in the progression of precancerous oral submucous fibrosis (OSF) remains to be elucidated.

Methods: Quantitative real-time PCR were used to examine the expression of GAS5-AS1 in OSF tissues. The activities of myofibroblasts, including collagen contractility and cell migration, as well as the marker α-smooth muscle actin (SMA) were assessed following overexpression of GAS5-AS1. Also, we analyzed the expression of Smad activity in order to gain insight into the downstream regulator.

Results: The level of GAS5-AS1 was found significantly downregulated in the OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs). Ectopic expression of GAS5-AS1 significantly reduced the abilities of collagen gel contraction and migration in fBMFs or arecoline-treated BMFs. Moreover, we have shown that overexpression of GAS5-AS1 inhibited the expression of p-Smad and the marker of myofibroblasts.

Conclusion: We showed the reduced expression of GAS5-AS1 in OSF tissues and demonstrated its effect on the myofibroblast activities and the level of p-Smad and α-SMA, indicating its potential contribution in OSF pathogenesis.

Keywords: Myofibroblasts; Oral submucous fibrosis; lncRNA GAS5-AS1.

MeSH terms

  • Arecoline / pharmacology
  • Cell Culture Techniques
  • Cell Movement
  • Down-Regulation
  • Humans
  • Mouth Mucosa / pathology*
  • Myofibroblasts / metabolism*
  • Oral Submucous Fibrosis / genetics*
  • Oral Submucous Fibrosis / metabolism
  • RNA, Long Noncoding / genetics*

Substances

  • GAS5 long non-coding RNA, human
  • RNA, Long Noncoding
  • Arecoline