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Stepwise crosstalk between aberrant Nf1, Tp53 and Rb signalling pathways induces gliomagenesis in zebrafish

文献类型：期刊论文

作者Luo, Juanjuan2,3; Liu, Pei2; Lu, Chunjiao2; Bian, Wanping3; Su, Dongsheng2,3; Zhu, Chenchen2; Xie, Shaolin3; Pan, Yihang1; Li, Ningning1; Cui, Wei4
刊名BRAIN
出版日期2021-02-01
卷号144页码:615-635
关键词nf1 rb1 tp53 glioma zebrafish
ISSN号0006-8950
DOI10.1093/brain/awaa430
通讯作者Pei, De-Sheng(peids@cigit.ac.cn) ; Yang, Xiaojun(yangx@stu.edu.cn)
英文摘要The molecular pathogenesis of glioblastoma indicates that RTK/Ras/PI3K, RB and TP53 pathways are critical for human glioma-genesis. Here, several transgenic zebrafish lines with single or multiple deletions of nf1, tp53 and rb1 in astrocytes, were established to genetically induce gliomagenesis in zebrafish. In the mutant with a single deletion, we found only the nf1 mutation low-efficiently induced tumour incidence, suggesting that the Nf1 pathway is critical for the initiation of gliomagenesis in zebrafish. Combination of mutations, nf1;tp53 and rb1;tp53 combined knockout fish, showed much higher tumour incidences, high-grade histology, increased invasiveness, and shortened survival time. Further bioinformatics analyses demonstrated the alterations in RTK/Ras/PI3K, cell cycle, and focal adhesion pathways, induced by abrogated nf1, tp53, or rb1, were probably the critical stepwise biological events for the initiation and development of gliomagenesis in zebrafish. Gene expression profiling and histological analyses showed the tumours derived from zebrafish have significant similarities to the subgroups of human gliomas. Furthermore, temozolomide treatment effectively suppressed gliomagenesis in these glioma zebrafish models, and the histological responses in temozolomide-treated zebrafish were similar to those observed in clinically treated glioma patients. Thus, our findings will offer a potential tool for genetically investigating gliomagenesis and screening potential targeted anti-tumour compounds for glioma treatment.
资助项目National Natural Science Foundation of China[81572494] ; National Natural Science Foundation of China[81872070] ; Natural Science Foundation of Guangdong Province[2015A030313440] ; Shantou University ; Projects of Chongqing Science and Technology Committee[cstc2019jcyj-zdxmX0035] ; Projects of Chongqing Science and Technology Committee[CSTCCXLJRC201714] ; Sanming Project of Medicine in Shenzhen[SZSM201911003] ; Technion-Israel Institute of Technology
WOS研究方向Neurosciences & Neurology
语种英语
WOS记录号WOS:000649446500034
出版者OXFORD UNIV PRESS
源URL[http://119.78.100.138/handle/2HOD01W0/13562]  
专题中国科学院重庆绿色智能技术研究院
通讯作者Pei, De-Sheng; Yang, Xiaojun
作者单位1.Sun Yat Sen Univ, Affiliated Hosp 7, Shenzhen 518107, Peoples R China
2.Shantou Univ, Neurosci Ctr, Med Coll, Shantou 515041, Peoples R China
3.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China
4.Shenyang Pharmaceut Univ, Dept Pharmacol, Coll Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China
推荐引用方式
GB/T 7714		 Luo, Juanjuan,Liu, Pei,Lu, Chunjiao,et al. Stepwise crosstalk between aberrant Nf1, Tp53 and Rb signalling pathways induces gliomagenesis in zebrafish[J]. BRAIN,2021,144:615-635.
APA Luo, Juanjuan.,Liu, Pei.,Lu, Chunjiao.,Bian, Wanping.,Su, Dongsheng.,...&Yang, Xiaojun.(2021).Stepwise crosstalk between aberrant Nf1, Tp53 and Rb signalling pathways induces gliomagenesis in zebrafish.BRAIN,144,615-635.
MLA Luo, Juanjuan,et al."Stepwise crosstalk between aberrant Nf1, Tp53 and Rb signalling pathways induces gliomagenesis in zebrafish".BRAIN 144(2021):615-635.

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来源：重庆绿色智能技术研究院

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