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

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

  • Oncogene. 2018 Apr;37(15):1961-1975. doi: 10.1038/s41388-017-0089-8.
Huichun Liang 1 2,  Ji Xiao 3,  Zhongmei Zhou 1,  Jiao Wu 4,  Fei Ge 5,  Zongcheng Li 6,  Hailin Zhang 1,  Jian Sun 3,  Fubing Li 1 2,  Rong Liu 7,  Ceshi Chen 8
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 2 University of the Chinese Academy of Sciences, Beijing, China.
  • 3 Medical Faculty of Kunming University of Science and Technology, Kunming, China.
  • 4 Department of the Second Medical Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 5 Department of the Breast Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 6 State Key Laboratory of Proteomics, Translational Medicine Center of Stem Cells, 307-lvy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing, China.
  • 7 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. liurong@mail.kiz.ac.cn.
  • 8 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. chenc@mail.kiz.ac.cn.
PMID: 29367761 DOI: 10.1038/s41388-017-0089-8
Abstract

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.

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