Research output: Contribution to journal › Article › Academic › peer-review
Long non-coding RNA MEG8 induces endothelial barrier through regulation of microRNA-370 and -494 processing. / Kremer, Veerle; Stanicek, Laura; van Ingen, Eva et al.
In: Journal of cell science, Vol. 135, No. 12, 15.06.2022.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Long non-coding RNA MEG8 induces endothelial barrier through regulation of microRNA-370 and -494 processing
AU - Kremer, Veerle
AU - Stanicek, Laura
AU - van Ingen, Eva
AU - Bink, Diewertje I.
AU - Hilderink, Sarah
AU - Tijsen, Anke J.
AU - Wittig, Ilka
AU - Mägdefessel, Lars
AU - Nossent, Anne Yaël
AU - Boon, Reinier A.
N1 - Funding Information: This study was supported by the Rembrandt Institute of Cardiovascular Science (to RAB and AYN), German Centre for Cardiovascular Research (to RAB), The Deutsche Forschungsgemeinschaft (TRR267/Z02 to IW, TRR267/B04 to RAB and LM) the European Research Council (“NOVA” and “NICCA” grants, to RAB), the Netherlands Organisation for Scientific Research (NWO Vidi, to RAB) and the European Union (Horizon 2020 Grant No. 825670, to RAB). Publisher Copyright: © 2022. Published by The Company of Biologists Ltd.
PY - 2022/6/15
Y1 - 2022/6/15
N2 - 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.
AB - 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.
KW - Aging
KW - Endothelial barrier
KW - Posttranscriptional modification
KW - non-coding RNA
UR - http://www.scopus.com/inward/record.url?scp=85132452119&partnerID=8YFLogxK
U2 - 10.1242/jcs.259671
DO - 10.1242/jcs.259671
M3 - Article
C2 - 35611612
VL - 135
JO - Journal of cell science
JF - Journal of cell science
SN - 0021-9533
IS - 12
ER -
ID: 25225097