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

Chih Yuan Fang, Cheng Chia Yu, Yi Wen Liao, Pei Ling Hsieh, Ming Yi Lu, Kuan Chou Lin, Ching Zong Wu, Lo Lin Tsai

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalJournal of Oral Pathology and Medicine
Volume48
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Keywords

  • arecoline
  • LINC00974
  • myofibroblasts
  • oral submucous fibrosis
  • TGF-β signaling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oral Surgery
  • Otorhinolaryngology
  • Cancer Research
  • Periodontics

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