LncRNA LINC00974 activates TGF‐β/Smad signaling to promote oral fibrogenesis

Abstract

Background Oral submucous fibrosis (OSF) is a progressive scarring disease and has been considered as a premalignant condition of the oral cavity. However, the detailed molecular mechanisms underlying the pathogenesis of OSF are still unclear. Method Here, we examined the expression of a novel long non‐coding RNA LINC00974 in OSF and investigated its function role in myofibroblast transdifferentiation. Phenotypic analyses, including collagen gel contraction, migration, invasion and wound healing assays, were used to assess the myofibroblast activities following overexpression or inhibition of LINC00974. Results We found that the expression of LINC00974 in OSF tissues or myofibroblasts was aberrantly upregulated, and there was a positive correlation between LINC00974 and myofibroblast markers. Our results showed that inhibition of LINC00974 suppressed the myofibroblast activities, while overexpression of LINC00974 increased the activation. We demonstrated that the expression levels of α‐SMA, α‐1 type I collagen, fibronectin were downregulated in the LINC00974‐inhibited myofibroblasts. Additionally, the TGF‐β secretion and phosphorylated Smad2 expression were also repressed in the LINC00974‐inhibited myofibroblasts. We further demonstrated that silence of LINC00974 prevented the arecoline‐induced myofibroblast activation, and LINC00974‐increased myofibroblast activities were via TGF‐β pathway. Conclusion Altogether, these findings suggested that arecoline‐increased myofibroblast transdifferentiation was via LINC00974‐mediated activation of TGF‐β signaling.

Arctigenin Reduces Myofibroblast Activities in Oral Submucous Fibrosis by LINC00974 Inhibition

“…In accordance with this finding, the protein expression level of phosphorylated Smad2 was downregulated, as well as myofibroblast marker α-SMA, extracellular cell matrix (ECM) molecules, and type I collagen A1, (Col1a1), following arctigenin administration (Figure 6B). Our recent work has demonstrated that long non-coding RNA LINC00974 activates TGF-β/Smad signaling to promote oral fibrogenesis [19]. We found that the TGF-β production and phosphorylated Smad2 expression were repressed in the LINC00974-inhibited myofibroblasts [19].…”

Oral Submucous Fibrosis: A Review on Etiopathogenesis, Diagnosis, and Therapy

“…In contrast, LINC00974 had the opposite effects. LINC00974 was aberrantly upregulated in OSF tissues and myofibroblasts [90].…”

Long non‑coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma (Review)

“…Research into lncRNAs has increased in the last 5 years; however, the function of numerous lncRNAs in OSF remains unclear. To date, only four articles have illustrated the relative issues (72)(73)(74)(75).…”

“…Fang et al (74), determined that arecoline-induced myof ibroblast t ra ns-di fferentiation occu r red via LINC00974-mediated activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway. According to their study, collagen gel contractility and myofibroblast migration ability was increased in fibrotic buccal mucosal fibroblasts (fBMFs) overexpressing LINC00974.…”