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

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

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.
原文英語
期刊Journal of Oral Pathology and Medicine
DOIs
出版狀態已發佈 - 2019

指紋

Myofibroblasts
Oral Submucous Fibrosis
Arecoline
Long Noncoding RNA
Collagen Type I
Fibronectins
Wound Healing
Cicatrix
Mouth
Collagen
Down-Regulation
Gels

ASJC Scopus subject areas

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

引用此文

@article{a5aaf097a55d4947b47ec1213b201209,
title = "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.",
keywords = "arecoline, LINC00974, myofibroblasts, oral submucous fibrosis, TGF-β signaling",
author = "Fang, {Chih Yuan} and Yu, {Cheng Chia} and Liao, {Yi Wen} and Hsieh, {Pei Ling} and Lu, {Ming Yi} and Lin, {Kuan Chou} and Wu, {Ching Zong} and Tsai, {Lo Lin}",
year = "2019",
doi = "10.1111/jop.12805",
language = "English",
journal = "Journal of Oral Pathology and Medicine",
issn = "0904-2512",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - LncRNA LINC00974 activates TGF-β/Smad signaling to promote oral fibrogenesis

AU - Fang, Chih Yuan

AU - Yu, Cheng Chia

AU - Liao, Yi Wen

AU - Hsieh, Pei Ling

AU - Lu, Ming Yi

AU - Lin, Kuan Chou

AU - Wu, Ching Zong

AU - Tsai, Lo Lin

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - arecoline

KW - LINC00974

KW - myofibroblasts

KW - oral submucous fibrosis

KW - TGF-β signaling

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U2 - 10.1111/jop.12805

DO - 10.1111/jop.12805

M3 - Article

AN - SCOPUS:85058055836

JO - Journal of Oral Pathology and Medicine

JF - Journal of Oral Pathology and Medicine

SN - 0904-2512

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