The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions

doi:10.1038/s41419-020-03150-0

	The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions
	Wang, Pan 1,5; Yan, Qian 5; Liao, Bin 5; Zhao, Lu 5; Xiong, Shuanglong 2; Wang, Junwei 5; Zou, Dewei 5; Pan, Jinyu 5; Wu, Liangqi 3,4; Deng, Yangmin 5
刊名	CELL DEATH & DISEASE
	2020-11-18
卷号	11 期号:11 页码:13
ISSN号	2041-4889
DOI	10.1038/s41419-020-03150-0
通讯作者	Wu, Nan(wunan881@tmmu.edu.cn) ; Gong, Sheng(Gongsheng@tmmu.edu.cn)
英文摘要	Hypoxia-inducible factor 1 alpha (HIF1 alpha) promotes the malignant progression of glioblastoma under hypoxic conditions, leading to a poor prognosis for patients with glioblastoma; however, none of the therapies targeting HIF1 alpha in glioblastoma have successfully eradicated the tumour. Therefore, we focused on the reason and found that treatments targeting HIF1 alpha and HIF2 alpha simultaneously increased tumour volume, but the combination of HIF1 alpha/HIF2 alpha-targeted therapies with temozolomide (TMZ) reduced tumourigenesis and significantly improved chemosensitization. Moreover, miR-210-3p induced HIF1 alpha expression but inhibited HIF2 alpha expression, suggesting that miR-210-3p regulates HIF1 alpha/HIF2 alpha expression. Epidermal growth factor (EGF) has been shown to upregulate HIF1 alpha expression under hypoxic conditions. However, in the present study, in addition to the signalling pathways mentioned above, the upstream proteins HIF1 alpha and HIF2 alpha have been shown to induce EGF expression by binding to the sequences AGGCGTGG and GGGCGTGG. Briefly, in a hypoxic microenvironment the HIF1 alpha/HIF2 alpha-miR210-3p network promotes the malignant progression of glioblastoma through a positive feedback loop with EGF. Additionally, differentiated glioblastoma cells underwent dedifferentiation to produce glioma stem cells under hypoxic conditions, and simultaneous knockout of HIF1 alpha and HIF2 alpha inhibited cell cycle arrest but promoted proliferation with decreased stemness, promoting glioblastoma cell chemosensitization. In summary, both HIF1 alpha and HIF2 alpha regulate glioblastoma cell proliferation, dedifferentiation and chemoresistance through a specific pathway, which is important for glioblastoma treatments.
资助项目	National Natural Science Foundation of China[NSFC 81802510] ; National Natural Science Foundation of China[81672493] ; Key Laboratory of Tumour Immunology of the Ministry of Education[2018sjz103]
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000591003200001
内容类型	期刊论文
源URL	[http://119.78.100.138/handle/2HOD01W0/12285]
专题	中国科学院重庆绿色智能技术研究院
通讯作者	Wu, Nan; Gong, Sheng
作者单位	1.Chongqing Med Univ, Chongqing 400016, Peoples R China 2.Chongqing Univ, Dept Oncol, Canc Hosp, Chongqing 400030, Peoples R China 3.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Univ Chinese Acad Sci, Chongqing Gen Hosp, Dept Neurosurg, Chongqing 401147, Peoples R China
推荐引用方式 GB/T 7714	Wang, Pan,Yan, Qian,Liao, Bin,et al. The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions[J]. CELL DEATH & DISEASE,2020,11(11):13.
APA	Wang, Pan.,Yan, Qian.,Liao, Bin.,Zhao, Lu.,Xiong, Shuanglong.,...&Gong, Sheng.(2020).The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions.CELL DEATH & DISEASE,11(11),13.
MLA	Wang, Pan,et al."The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions".CELL DEATH & DISEASE 11.11(2020):13.