GAS5 decreased the arecoline-induced myofibroblasts activity in buccal mucosal fibroblasts via acting as a competing endogenous RNA for miR-21

Background/purpose

Oral submucous fibrosis (OSF) is recognized as a premalignant condition that increases the risk of oral cancer. Myofibroblasts are the primary cellular mediators of the pathological fibrosis characteristic of OSF. Consequently, understanding the molecular mechanisms that drive myofibroblast activation is crucial for the development of effective therapeutic interventions for this condition. Growth arrest-specific 5 (GAS5), a long non-coding RNA, represents a potential regulatory factor in OSF pathogenesis, although its specific role remains largely undefined.

Materials and methods

To validate the direct interaction between GAS5 and its target miR-21, a luciferase reporter assay was performed. qRT-PCR was employed to evaluate the expression levels of GAS5 in OSF tissues. Collagen gel contraction and transwell migration assays were utilized to assess myofibroblast functional activities.

Results

Our result validated overexpression of GAS5 inhibits TGF-β-induced myofibroblast activation, as evidenced by reduced collagen gel contraction, cell migration, and suppression of the TGF-β/Smad2 signaling pathway. GAS5 also attenuates arecoline-induced myofibroblast activation. Mechanistically, GAS5 directly interacts with and sponges miR-21, thereby modulating myofibroblast function.

Conclusion

Our findings suggest that GAS5 plays a crucial role in inhibiting myofibroblast activation in OSF by targeting the TGF-β/Smad2 signaling pathway and regulating the miR-21. GAS5 may represent a novel therapeutic target for the prevention and treatment of OSF.