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

Veerle Kremer, Laura Stanicek, Eva van Ingen, Diewertje I. Bink, Sarah Hilderink, Anke J. Tijsen, Ilka Wittig, Lars Mägdefessel, Anne Yaël Nossent, Reinier A. Boon

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3 Citations (Scopus)

Abstract

The 14q32 locus is an imprinted region in the human genome which contains multiple noncoding RNAs. We investigated the role of Maternally Expressed Gene 8 (MEG8) in endothelial function and the underlying mechanism. A 5-fold increase in MEG8 was observed with increased passage number in Human Umbilical Vein Endothelial Cells, suggesting MEG8 is induced during aging. MEG8 knockdown resulted in a 1.8-fold increase in senescence, suggesting MEG8 might be protective during aging. Endothelial barrier was impaired after MEG8 silencing. MEG8 knockdown resulted in reduced expression of miRNA-370 and -494 but not -127, -487b and -410. Overexpression of miRNA-370/-494 partially rescued MEG8-silencing-induced barrier loss. Mechanistically, MEG8 regulates expression of miRNA-370 and -494 at the mature miRNA level through interaction with RNA binding proteins Cold Inducible RNA Binding Protein (CIRBP) and Hydroxyacyl-CoA Dehydrogenase Trifunctional Multi-enzyme Complex Subunit Beta (HADHB). Precursor and mature miRNA-370/-494 were shown to interact with HADHB and CIRBP respectively. CIRBP/HADHB silencing resulted in downregulation of miRNA-370 and induction of miRNA-494. These results suggest MEG8 interacts with CIRBP and HADHB and contributes to miRNA processing at the post-transcriptional level.

Original languageEnglish
JournalJournal of Cell Science
Volume135
Issue number12
DOIs
Publication statusPublished - 15 Jun 2022

Keywords

  • Aging
  • Endothelial barrier
  • Posttranscriptional modification
  • non-coding RNA

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