MiR-492 impairs the angiogenic potential of endothelial cells

TY - JOUR

T1 - MiR-492 impairs the angiogenic potential of endothelial cells

AU - Patella, Francesca

AU - Leucci, Eleonora

AU - Evangelista, Monica

AU - Parker, Brian

AU - Wen, Jiayu

AU - Mercatanti, Alberto

AU - Rizzo, Milena

AU - Chiavacci, Elena

AU - Lund, Anders H.

AU - Rainaldi, Giuseppe

N1 - © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

PY - 2013/8

Y1 - 2013/8

N2 - Endothelial cells growing in high glucose-containing medium show reduced cell proliferation and in vitro angiogenesis. Evidence suggests that the molecular pathways leading to these cellular responses are controlled by microRNAs, endogenous post-transcriptional regulators of gene expression. To identify the microRNAs and their targeted genes involved in the glucose responses, we performed the miRNA signature of Human Umbelical Vein Endothelial Cells (HUVECs) exposed and unexposed to high glucose. Among differentially expressed microRNAs, we analysed miR-492 and showed that its overexpression was able to reduce proliferation, migration and tube formation of HUVEC. These effects were accompanied by the down-regulation of eNOS, a key regulator of the endothelial cell function. We showed that eNOS was indirectly down-regulated by miR-492 and we discovered that miR-492 was able to bind mRNAs involved in proliferation, migration, tube formation and regulation of eNOS activity and expression. Moreover, we found that miR-492 decreased VEGF expression in HUVEC and impaired in vivo angiogenesis in a tumour xenograft model, suggesting a role also in modulating the secretion of pro-angiogenic factors. Taken together, the data indicate that miR-492 exerts a potent anti-angiogenic activity in endothelial cells and therefore miR-492 seems a promising tool for anti-angiogenic therapy.

AB - Endothelial cells growing in high glucose-containing medium show reduced cell proliferation and in vitro angiogenesis. Evidence suggests that the molecular pathways leading to these cellular responses are controlled by microRNAs, endogenous post-transcriptional regulators of gene expression. To identify the microRNAs and their targeted genes involved in the glucose responses, we performed the miRNA signature of Human Umbelical Vein Endothelial Cells (HUVECs) exposed and unexposed to high glucose. Among differentially expressed microRNAs, we analysed miR-492 and showed that its overexpression was able to reduce proliferation, migration and tube formation of HUVEC. These effects were accompanied by the down-regulation of eNOS, a key regulator of the endothelial cell function. We showed that eNOS was indirectly down-regulated by miR-492 and we discovered that miR-492 was able to bind mRNAs involved in proliferation, migration, tube formation and regulation of eNOS activity and expression. Moreover, we found that miR-492 decreased VEGF expression in HUVEC and impaired in vivo angiogenesis in a tumour xenograft model, suggesting a role also in modulating the secretion of pro-angiogenic factors. Taken together, the data indicate that miR-492 exerts a potent anti-angiogenic activity in endothelial cells and therefore miR-492 seems a promising tool for anti-angiogenic therapy.

U2 - 10.1111/jcmm.12085

DO - 10.1111/jcmm.12085

M3 - Journal article

C2 - 23802567

SN - 1582-1838

VL - 17

SP - 1006

EP - 1015

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

IS - 8

ER -