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Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis

It is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. In this study, we demonstrated that miR-153 directly inh... Full description

Journal Title: Oncogene April 2018, Vol.37(15), pp.1961-1975
Main Author: Liang, Huichun
Other Authors: Xiao, Ji , Zhou, Zhongmei , Wu, Jiao , Ge, Fei , Li, Zongcheng , Zhang, Hailin , Sun, Jian , Li, Fubing , Liu, Rong , Chen, Ceshi
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1476-5594 ; PMID: 29367761 Version:1 ; DOI: 10.1038/s41388-017-0089-8
Link: http://pubmed.gov/29367761
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recordid: medline29367761
title: Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis
format: Article
creator:
  • Liang, Huichun
  • Xiao, Ji
  • Zhou, Zhongmei
  • Wu, Jiao
  • Ge, Fei
  • Li, Zongcheng
  • Zhang, Hailin
  • Sun, Jian
  • Li, Fubing
  • Liu, Rong
  • Chen, Ceshi
subjects:
  • Breast Neoplasms
  • Endoribonucleases -- Physiology
  • Micrornas -- Genetics
  • Neovascularization, Pathologic -- Genetics
  • Protein-Serine-Threonine Kinases -- Physiology
  • Tumor Hypoxia -- Genetics
  • X-Box Binding Protein 1 -- Physiology
ispartof: Oncogene, April 2018, Vol.37(15), pp.1961-1975
description: It is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. In this study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3'UTR of HIF1A mRNA, as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor X-box binding protein 1 (XBP1). X-box binding protein 1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These results indicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy.
language: eng
source:
identifier: E-ISSN: 1476-5594 ; PMID: 29367761 Version:1 ; DOI: 10.1038/s41388-017-0089-8
fulltext: fulltext
issn:
  • 14765594
  • 1476-5594
url: Link


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titleHypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis
creatorLiang, Huichun ; Xiao, Ji ; Zhou, Zhongmei ; Wu, Jiao ; Ge, Fei ; Li, Zongcheng ; Zhang, Hailin ; Sun, Jian ; Li, Fubing ; Liu, Rong ; Chen, Ceshi
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subjectBreast Neoplasms ; Endoribonucleases -- Physiology ; Micrornas -- Genetics ; Neovascularization, Pathologic -- Genetics ; Protein-Serine-Threonine Kinases -- Physiology ; Tumor Hypoxia -- Genetics ; X-Box Binding Protein 1 -- Physiology
descriptionIt is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. In this study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3'UTR of HIF1A mRNA, as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor X-box binding protein 1 (XBP1). X-box binding protein 1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These results indicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy.
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descriptionIt is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. In this study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3'UTR of HIF1A mRNA, as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor X-box binding protein 1 (XBP1). X-box binding protein 1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These results indicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy.
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abstractIt is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1α)/vascular endothelial growth factor A (VEGFA) axis to promote angiogenesis in breast cancer. However, it is unclear how this axis is negatively regulated. In this study, we demonstrated that miR-153 directly inhibits expression of HIF1α by binding to the 3'UTR of HIF1A mRNA, as well as suppresses tube formation of primary human umbilical vein endothelial cells (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA. Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress, which activates IRE1α and its downstream transcription factor X-box binding protein 1 (XBP1). X-box binding protein 1 directly binds to the promoter of the miR-153 host gene PTPRN and activates transcription. These results indicate that hypoxia induces miR-153 to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy.
doi10.1038/s41388-017-0089-8
pmid29367761
issn09509232
oafree_for_read
date2018-04