Work

Silencing miR-1291-LEFTY2 axis diminishes the myofibroblast activities and reactive oxygen species generation of fibrotic buccal mucosal fibroblasts

Year: 2025

Type: article

Abstract: Background/purpose: Oral submucous fibrosis (OSF) is a potentially malignant disorder characterized by chronic inflammation and excessive collagen deposition, leading to fibrosis in the oral mucosa. This study aimed to explore the contribution of the miR-1291/LEFTY2 axis in the development of OSF progression. Materials and methods: Expression of miR-1291 was evaluated in OSF tissues and primary myofibroblasts using RNA sequencing and qRT-PCR. The functional role of miR-1291 and LEFTY2 were investigated using miR-1291 inhibitor and lentiviral-mediated overexpression of LEFTY2, respectively. A luciferase reporter assay was conducted to examine the direct interaction between miR-1291 and LEFTY2. Myofibroblast activities were assessed by collagen gel contraction, wound healing, and transwell migration assays. Reactive oxygen species (ROS) production was measured by flow cytometry. Results: MiR-1291 was markedly upregulated in OSF tissues and myofibroblasts, and it was positively correlated with a couple of fibrosis markers, including α-SMA and TGF-β1. Inhibition of miR-1291 suppressed myofibroblast activities and ROS generation. Luciferase reporter assays confirmed that miR-1291 is directly bound to the three prime untranslated region (3'UTR) of LEFTY2, a negative regulator of TGF-β signaling. Overexpression of LEFTY2 attenuated phosphorylation of Smad, myofibroblast activities, and ROS production. Conclusion: Our findings demonstrated that miR-1291 may promote fibrosis in OSF by suppressing LEFTY2 expression to increase myofibroblast activation via regulation of ROS accumulation and TGF-β/Smad signaling.

Source: Journal of Dental Sciences

DOI: 10.1016/j.jds.2025.03.019

Authors: Ming-Yung Chou, Shih-Min Wang, Pei-Ling Hsieh, Yi-Wen Liao, Cheng-Chia Yu, Chang-Yi Tsai