MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells

Hyejeong Kim, Yeongrim Ko, Hyojin Park, Haiying Zhang, Yoonjeong Jeong, Yeomyeong Kim, Minyoung Noh, Songyi Park, Young Myeong Kim, Young Guen Kwon

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior. Overexpression of miR-148a/b-3p in ECs significantly reduced migration, filamentous actin remodeling, and angiogenic sprouting. Intriguingly, the effects of decreased miR-148a/b-3p levels were augmented by treatment with vascular endothelial growth factor (VEGF). Importantly, we found that miR-148a/b-3p directly regulated neuropilin-1 (NRP1) expression by binding to its 3′-untranslated region. In addition, because NRP1 is the coreceptor for VEGF receptor 2 (VEGFR2), overexpression of miR-148a/b-3p inhibited VEGF-induced activation of VEGFR2 and inhibited its downstream pathways, as indicated by changes to phosphorylated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase. Collectively, our results demonstrate that miR-148a/b-3p is a direct transcriptional regulator of NRP1 that mediates antiangiogenic pathways. These data suggest that miR-148a/b-3p is a therapeutic candidate for overcoming EC dysfunction and angiogenic disorders, including ischemia, retinopathy, and tumor vascularization.

Original languageEnglish
Article number134
JournalExperimental and Molecular Medicine
Volume51
Issue number11
DOIs
Publication statusPublished - 2019 Nov 1

Fingerprint

Neuropilin-1
Endothelial cells
MicroRNAs
Endothelial Cells
Vascular Endothelial Growth Factor A
RNA Sequence Analysis
Vascular Endothelial Growth Factor Receptor-2
Focal Adhesion Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor Receptor
Extracellular Signal-Regulated MAP Kinases
3' Untranslated Regions
p38 Mitogen-Activated Protein Kinases
Fetal Blood
Actins
Tumors
Blood Cells
Blood
Down-Regulation
Ischemia
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Kim, Hyejeong ; Ko, Yeongrim ; Park, Hyojin ; Zhang, Haiying ; Jeong, Yoonjeong ; Kim, Yeomyeong ; Noh, Minyoung ; Park, Songyi ; Kim, Young Myeong ; Kwon, Young Guen. / MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells. In: Experimental and Molecular Medicine. 2019 ; Vol. 51, No. 11.
@article{0a624e7cd8dc40678e6fcf10d5f2fb63,
title = "MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells",
abstract = "MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior. Overexpression of miR-148a/b-3p in ECs significantly reduced migration, filamentous actin remodeling, and angiogenic sprouting. Intriguingly, the effects of decreased miR-148a/b-3p levels were augmented by treatment with vascular endothelial growth factor (VEGF). Importantly, we found that miR-148a/b-3p directly regulated neuropilin-1 (NRP1) expression by binding to its 3′-untranslated region. In addition, because NRP1 is the coreceptor for VEGF receptor 2 (VEGFR2), overexpression of miR-148a/b-3p inhibited VEGF-induced activation of VEGFR2 and inhibited its downstream pathways, as indicated by changes to phosphorylated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase. Collectively, our results demonstrate that miR-148a/b-3p is a direct transcriptional regulator of NRP1 that mediates antiangiogenic pathways. These data suggest that miR-148a/b-3p is a therapeutic candidate for overcoming EC dysfunction and angiogenic disorders, including ischemia, retinopathy, and tumor vascularization.",
author = "Hyejeong Kim and Yeongrim Ko and Hyojin Park and Haiying Zhang and Yoonjeong Jeong and Yeomyeong Kim and Minyoung Noh and Songyi Park and Kim, {Young Myeong} and Kwon, {Young Guen}",
year = "2019",
month = "11",
day = "1",
doi = "10.1038/s12276-019-0344-x",
language = "English",
volume = "51",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "11",

}

MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells. / Kim, Hyejeong; Ko, Yeongrim; Park, Hyojin; Zhang, Haiying; Jeong, Yoonjeong; Kim, Yeomyeong; Noh, Minyoung; Park, Songyi; Kim, Young Myeong; Kwon, Young Guen.

In: Experimental and Molecular Medicine, Vol. 51, No. 11, 134, 01.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells

AU - Kim, Hyejeong

AU - Ko, Yeongrim

AU - Park, Hyojin

AU - Zhang, Haiying

AU - Jeong, Yoonjeong

AU - Kim, Yeomyeong

AU - Noh, Minyoung

AU - Park, Songyi

AU - Kim, Young Myeong

AU - Kwon, Young Guen

PY - 2019/11/1

Y1 - 2019/11/1

N2 - MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior. Overexpression of miR-148a/b-3p in ECs significantly reduced migration, filamentous actin remodeling, and angiogenic sprouting. Intriguingly, the effects of decreased miR-148a/b-3p levels were augmented by treatment with vascular endothelial growth factor (VEGF). Importantly, we found that miR-148a/b-3p directly regulated neuropilin-1 (NRP1) expression by binding to its 3′-untranslated region. In addition, because NRP1 is the coreceptor for VEGF receptor 2 (VEGFR2), overexpression of miR-148a/b-3p inhibited VEGF-induced activation of VEGFR2 and inhibited its downstream pathways, as indicated by changes to phosphorylated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase. Collectively, our results demonstrate that miR-148a/b-3p is a direct transcriptional regulator of NRP1 that mediates antiangiogenic pathways. These data suggest that miR-148a/b-3p is a therapeutic candidate for overcoming EC dysfunction and angiogenic disorders, including ischemia, retinopathy, and tumor vascularization.

AB - MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior. Overexpression of miR-148a/b-3p in ECs significantly reduced migration, filamentous actin remodeling, and angiogenic sprouting. Intriguingly, the effects of decreased miR-148a/b-3p levels were augmented by treatment with vascular endothelial growth factor (VEGF). Importantly, we found that miR-148a/b-3p directly regulated neuropilin-1 (NRP1) expression by binding to its 3′-untranslated region. In addition, because NRP1 is the coreceptor for VEGF receptor 2 (VEGFR2), overexpression of miR-148a/b-3p inhibited VEGF-induced activation of VEGFR2 and inhibited its downstream pathways, as indicated by changes to phosphorylated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase. Collectively, our results demonstrate that miR-148a/b-3p is a direct transcriptional regulator of NRP1 that mediates antiangiogenic pathways. These data suggest that miR-148a/b-3p is a therapeutic candidate for overcoming EC dysfunction and angiogenic disorders, including ischemia, retinopathy, and tumor vascularization.

UR - http://www.scopus.com/inward/record.url?scp=85074958581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074958581&partnerID=8YFLogxK

U2 - 10.1038/s12276-019-0344-x

DO - 10.1038/s12276-019-0344-x

M3 - Article

C2 - 31723119

AN - SCOPUS:85074958581

VL - 51

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 11

M1 - 134

ER -