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A positive feedback circuit comprising p21 and HIF-1 alpha aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis

文献类型：期刊论文

作者Jin, Xiaodong1,2,3,4,5; Kuang, Yanbei1,2,3,4; Li, Linying1,2,3,4; Li, Hongbin6; Zhao, Ting1,2,3,4; He, Yufang7; Di, Cuixia1,2,3,4,5; Kang, Jian8; Yuan, Lingyan1; Yu, Boyi1,2,3,4
刊名FASEB JOURNAL
出版日期2022-03-01
卷号36期号:3页码:14
ISSN号0892-6638
关键词glioblastoma glycolysis HIF-1 alpha hypoxia p21 radioresistance
DOI10.1096/fj.202101736R
通讯作者Li, Qiang(liqiang@impcas.ac.cn)
英文摘要The radioresistance induced by hypoxia is the major obstacle in the successful treatment of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, through which mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. In this study, we discovered a novel function of p21, which participated in the regulation of metabolic pathways under hypoxia. We found that p21 was upregulated in glioblastoma (GBM) cells under hypoxic conditions, which enhanced the radioresistance of GBM cells. In principle, HIF-1 alpha is bound directly to the hypoxia response elements (HREs) of the p21 promoter to enhance its transcription activity, in turn, p21 also promoted the transcription of HIF-1 alpha at the mRNA level and maintained HIF-1 alpha function under oxygen deficiency. The positive correlation between p21 and HIF-1 alpha augmented Glut1/LDHA-mediated glycolysis and aggravated the radioresistance of GBM cells. Thus, our results constructed a positive feedback circuit comprising p21/HIF-1 alpha that might play a key role in enhancing the radioresistance of GBM under hypoxia.
WOS关键词FUNCTIONAL INTERACTION ; RECIPROCAL REGULATION ; INDUCIBLE FACTOR ; DNA-DAMAGE ; CELL-DEATH ; CANCER ; GLIOMA ; RESISTANCE ; INHIBITOR ; RADIOSENSITIZATION
资助项目National Natural Science Foundation of China[11875299] ; National Natural Science Foundation of China[U1532264] ; National Key Research Program of China[2018YFC0115700] ; National Key Research Program of China[2018YFC0115702] ; Key Deployment Project of Chinese Academy of Sciences[KFZD-SW-222]
WOS研究方向Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种英语
出版者WILEY
WOS记录号WOS:000761250800015
资助机构National Natural Science Foundation of China ; National Key Research Program of China ; Key Deployment Project of Chinese Academy of Sciences
源URL[http://119.78.100.186/handle/113462/141927]  
专题中国科学院近代物理研究所
通讯作者Li, Qiang
作者单位1.Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Gansu, Peoples R China
2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China
3.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou, Gansu, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Lanhai Nucl Med Res Ctr, Putian, Peoples R China
6.Lanzhou Univ Technol, Sch Life Sci & Engn, Lanzhou, Peoples R China
7.Third Hosp Gansu Prov, Lanzhou, Peoples R China
8.Lanzhou Univ Technol, Coll Energy & Power Engn, Lanzhou, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Xiaodong,Kuang, Yanbei,Li, Linying,et al. A positive feedback circuit comprising p21 and HIF-1 alpha aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis[J]. FASEB JOURNAL,2022,36(3):14.
APA Jin, Xiaodong.,Kuang, Yanbei.,Li, Linying.,Li, Hongbin.,Zhao, Ting.,...&Li, Qiang.(2022).A positive feedback circuit comprising p21 and HIF-1 alpha aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis.FASEB JOURNAL,36(3),14.
MLA Jin, Xiaodong,et al."A positive feedback circuit comprising p21 and HIF-1 alpha aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis".FASEB JOURNAL 36.3(2022):14.

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来源：近代物理研究所

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