机构:[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外科科室普通外科普通外四科(乳腺外科)昆明医科大学附属第一医院[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
It is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha (HIF1 alpha)/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 HIF1 alpha 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 hypoxiastimulated ER stress, which activates IRE1 alpha 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 HIF1 alpha/VEGFA axis in breast cancer angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis therapy.
基金:
Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDA12010303]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31771516, U1502222, U1602221, 81772847, 81660438]; Yunnan Applied Basic Research Key Projects [2015FA027]
第一作者机构:[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
通讯作者:
推荐引用方式(GB/T 7714):
Liang Huichun,Xiao Ji,Zhou Zhongmei,et al.Hypoxia induces miR-153 through the IRE1 alpha-XBP1 pathway to fine tune the HIF1 alpha/VEGFA axis in breast cancer angiogenesis[J].ONCOGENE.2018,37(15):1961-1975.doi:10.1038/s41388-017-0089-8.
APA:
Liang, Huichun,Xiao, Ji,Zhou, Zhongmei,Wu, Jiao,Ge, Fei...&Chen, Ceshi.(2018).Hypoxia induces miR-153 through the IRE1 alpha-XBP1 pathway to fine tune the HIF1 alpha/VEGFA axis in breast cancer angiogenesis.ONCOGENE,37,(15)
MLA:
Liang, Huichun,et al."Hypoxia induces miR-153 through the IRE1 alpha-XBP1 pathway to fine tune the HIF1 alpha/VEGFA axis in breast cancer angiogenesis".ONCOGENE 37..15(2018):1961-1975