KMS Chongqing Institute of Green and Intelligent Technology, CAS
| The HIF1 alpha/HIF2 alpha-miR210-3p network regulates glioblastoma cell proliferation, dedifferentiation and chemoresistance through EGF under hypoxic conditions | |
| Wang, Pan1,2; Yan, Qian1; Liao, Bin1; Zhao, Lu1; Xiong, Shuanglong3; Wang, Junwei1; Zou, Dewei1; Pan, Jinyu1; Wu, Liangqi4,5; Deng, Yangmin1 | |
| 2020-11-18 | |
| 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. |
| DOI | 10.1038/s41419-020-03150-0 |
| 发表期刊 | CELL DEATH & DISEASE
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| ISSN | 2041-4889 |
| 卷号 | 11期号:11页码:13 |
| 通讯作者 | Wu, Nan(wunan881@tmmu.edu.cn) ; Gong, Sheng(Gongsheng@tmmu.edu.cn) |
| 收录类别 | SCI |
| WOS记录号 | WOS:000591003200001 |
| 语种 | 英语 |
