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Aberrantly downregulated FENDRR by arecoline elevates ROS and myofibroblast activation via mitigating the

Yi-Wen Liao1, Cheng-Chia Yu2, Chang-Wei Hsieh3

  • 1Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung 402, Taiwan.

International Journal of Biological Macromolecules
|March 5, 2024
PubMed

Insights

Long non-coding RNA FENDRR, crucial in oral submucous fibrosis (OSF), suppresses myofibroblast activation by regulating miR-214 and mitofusin 2. Its downregulation links to arecoline exposure, promoting OSF progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Fibrosis Research

Background:

  • Long non-coding RNA FENDRR exhibits anti-fibrotic and anti-cancer roles.
  • Its function in premalignant oral submucous fibrosis (OSF) is not well understood.

Purpose of the Study:

  • To investigate the role of FENDRR in oral submucous fibrosis (OSF) development.
  • To elucidate the molecular mechanism of FENDRR in myofibroblast transdifferentiation.

Main Methods:

  • Analysis of FENDRR expression in OSF tissues and cells.
  • Overexpression and knockdown studies of FENDRR.
  • RNA-binding assays to confirm FENDRR-miR-214 interaction.
  • Western blotting for MFN2 expression.
  • Assessment of reactive oxygen species (ROS) levels.

Main Results:

  • FENDRR was downregulated in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs).
  • FENDRR overexpression inhibited myofibroblast hallmarks, while its downregulation promoted them.
  • FENDRR directly targets miR-214, suppressing myofibroblast activation.
  • Mitofusin 2 (MFN2) is a direct target of miR-214; FENDRR positively correlates with MFN2.
  • The FENDRR/miR-214 axis influences arecoline-induced ROS accumulation and myofibroblast transdifferentiation.

Conclusions:

  • Aberrant FENDRR downregulation in OSF is linked to chronic arecoline exposure.
  • This downregulation promotes ROS and myofibroblast activation via miR-214-mediated MFN2 suppression.
  • FENDRR acts as a tumor suppressor in OSF by inhibiting myofibroblast activation.
Keywords:
Long non-coding RNA FENDRRMicroRNA-214Mitofusin 2

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