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Linc-RAM is required for FGF2 function in regulating myogenic cell differentiation.

Yixia Zhao1, Fengqi Cao1, Xiaohua Yu1

  • 1a The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences , Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College , 5 Dong Dan San Tiao, Beijing , China.

RNA Biology
|January 25, 2018
PubMed
Summary

Basic fibroblast growth factor (FGF2) represses Linc-RAM, a long non-coding RNA, via the Ras/Raf/Mek/Erk pathway. This repression is necessary for FGF2 to inhibit skeletal muscle stem cell differentiation.

Keywords:
FGF2Linc-RAMLong non-coding RNAMyoDmuscle cell differentiation

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Area of Science:

  • Muscle stem cell biology
  • Molecular and cellular biology
  • Epigenetics

Background:

  • Skeletal muscle stem cell differentiation is regulated by intrinsic and extrinsic factors.
  • Basic fibroblast growth factor (FGF2) inhibits differentiation by repressing MyoD.
  • Linc-RAM, a long non-coding RNA, enhances differentiation by facilitating MyoD/Baf60c/Brg1 complex formation.

Purpose of the Study:

  • To investigate the transcriptional regulation of Linc-RAM by FGF2.
  • To elucidate the intracellular signaling pathway mediating Linc-RAM gene expression.
  • To determine the functional role of Linc-RAM in FGF2-modulated muscle differentiation.

Main Methods:

  • Analysis of Linc-RAM promoter activity in C2C12 cells treated with FGF2.
  • Gene expression analysis in MyoD knockout satellite cells.
  • Overexpression studies of Linc-RAM in C2C12 cells.
  • Ex vivo culture of single muscle fibers.
  • Analysis of Linc-RAM knockout satellite cells.

Main Results:

  • FGF2 negatively regulates Linc-RAM expression via the Ras/Raf/Mek/Erk pathway.
  • MyoD overexpression attenuates FGF2-mediated repression of Linc-RAM.
  • MyoD knockout abolishes FGF2-mediated repression of Linc-RAM transcription.
  • Linc-RAM overexpression rescues FGF2-induced inhibition of myogenesis.
  • Linc-RAM inhibition is required for FGF2-mediated suppression of myogenic differentiation.

Conclusions:

  • FGF2 represses Linc-RAM through the Ras/Raf/Mek/Erk pathway, requiring MyoD inhibition.
  • Linc-RAM is essential for FGF2 to inhibit skeletal muscle stem cell differentiation.
  • This study reveals a novel regulatory mechanism of muscle differentiation involving Linc-RAM and FGF2 signaling.