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The long non-coding RNA MEG8 induces an endothelial barrier through regulation of microRNA-370 and -494 processing

Veerle Kremer1,2,3, Laura Stanicek1,2,4, Eva van Ingen5

  • 1Amsterdam UMC location Vrije Universiteit, Department of Physiology, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.

Journal of Cell Science
|May 25, 2022
PubMed

Insights

The long non-coding RNA MEG8 protects against endothelial aging and barrier dysfunction. It regulates microRNA-370 and -494 processing by interacting with RNA-binding proteins CIRBP and HADHB.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cell Biology

Background:

  • The 14q32 locus is an imprinted genomic region containing non-coding RNAs.
  • Endothelial aging is associated with impaired function and barrier integrity.
  • The role of long non-coding RNA maternally expressed gene 8 (MEG8) in endothelial cells is largely unknown.

Purpose of the Study:

  • To investigate the function of MEG8 in endothelial cells.
  • To elucidate the molecular mechanisms underlying MEG8's role in endothelial aging and barrier function.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were used to study MEG8 expression and function.
  • MEG8 knockdown and overexpression were performed to assess its effects on senescence and barrier integrity.
  • MicroRNA (miRNA) expression analysis and RNA-binding protein interactions were investigated using molecular biology techniques.

Main Results:

  • MEG8 expression increased with passage number in HUVECs, suggesting induction during aging.
  • MEG8 knockdown accelerated senescence and impaired endothelial barrier function.
  • MEG8 regulates the processing of miRNA-370 and miRNA-494 through interactions with CIRBP and HADHB at the post-transcriptional level.

Conclusions:

  • MEG8 plays a protective role in endothelial aging.
  • MEG8 is a key regulator of miRNA processing, influencing endothelial barrier function.
  • The interaction of MEG8 with CIRBP and HADHB is crucial for miRNA maturation and endothelial homeostasis.
Keywords:
AgingEndothelial barrierNon-coding RNAPost-transcriptional modification

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