FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway.
FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway.
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FLI 1通过TIE 1介导的PI 3 K/AKT信号通路调节鼻咽癌放疗抵抗
DOI：
10.1186/s12967-023-03986-y
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发表时间：
2023-02-22
影响因子：
7.4
通讯作者：
Xie, Fangyun
中科院分区：
文献类型：
--
作者：
Chen, Enni;Huang, Jiajia;Chen, Miao;Wu, Jiawei;Ouyang, Puyun;Wang, Xiaonan;Shi, Dingbo;Liu, Zhiqiao;Zhu, Wancui;Sun, Haohui;Yang, Shanshan;Zhang, Baoyu;Deng, Wuguo;Qiu, Huijuan;Xie, Fangyun
放射治疗抵抗是导致鼻咽癌治疗失败、预后不良的主要原因。因此，迫切需要阐明放疗抵抗的分子机制。将RNA-seq分析应用于五对进行性疾病（PD）和完全反应（CR）NPC组织。使用功能丧失和功能获得测定法在体外和体内测定FLI 1的致癌功能。进行RNA-seq分析、ChIP测定和双荧光素酶报告基因测定以探索FLI 1和TIE 1之间的相互作用。分析FLI 1/TIE 1表达与鼻咽癌预后的关系。FLI 1是一种潜在的放射敏感性调节因子，与CR患者相比，PD患者对放射治疗的过度表达显著增加。FLI 1在体外可诱导放疗抵抗，增强DNA损伤修复能力，在体内可促进放疗抵抗。机制研究表明FLI 1通过与TIE 1的启动子结合上调TIE 1的转录，从而激活PI 3 K/AKT信号通路。TIE 1表达的降低恢复了NPC细胞的放射敏感性。FLI 1和TIE 1高表达的鼻咽癌患者预后差。我们的研究表明，FLI 1通过TIE 1介导的PI 3 K/AKT信号通路调节鼻咽癌的放疗抵抗，提示靶向FLI 1/TIE 1信号通路可能是提高鼻咽癌放疗疗效的潜在治疗策略。在线版本包含补充材料，可通过10.1186/s12967-023-03986-y获得。
Radiotherapy resistance is the main cause of treatment failure in nasopharyngeal carcinoma (NPC), which leads to poor prognosis. It is urgent to elucidate the molecular mechanisms underlying radiotherapy resistance. RNA-seq analysis was applied to five paired progressive disease (PD) and complete response (CR) NPC tissues. Loss-and gain-of-function assays were used for oncogenic function of FLI1 both in vitro and in vivo. RNA-seq analysis, ChIP assays and dual luciferase reporter assays were performed to explore the interaction between FLI1 and TIE1. Gene expression with clinical information from tissue microarray of NPC were analyzed for associations between FLI1/TIE1 expression and NPC prognosis. FLI1 is a potential radiosensitivity regulator which was dramatically overexpressed in the patients with PD to radiotherapy compared to those with CR. FLI1 induced radiotherapy resistance and enhanced the ability of DNA damage repair in vitro, and promoted radiotherapy resistance in vivo. Mechanistic investigations showed that FLI1 upregulated the transcription of TIE1 by binding to its promoter, thus activated the PI3K/AKT signaling pathway. A decrease in TIE1 expression restored radiosensitivity of NPC cells. Furthermore, NPC patients with high levels of FLI1 and TIE1 were correlated with poor prognosis. Our study has revealed that FLI1 regulates radiotherapy resistance of NPC through TIE1-mediated PI3K/AKT signaling pathway, suggesting that targeting the FLI1/TIE1 signaling pathway could be a potential therapeutic strategy to enhance the efficacy of radiotherapy in NPC. The online version contains supplementary material available at 10.1186/s12967-023-03986-y.
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影响因子：
9
作者：
通讯作者：
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影响因子：
15.9
作者：
D'Amico, Gabriela;Korhonen, Emilia A.;Alitalo, Kari
通讯作者：
Alitalo, Kari
影响因子：
45.3
作者：
Fang, Fu-Min;Tsai, Wen-Ling;Lee, Chien-Hung
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Lee, Chien-Hung
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2.7
作者：
Aguayo, A;Manshouri, T;Albitar, M
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Albitar, M
DOI：
10.1097/00005072-199611000-00003
发表时间：
1996-11-01
影响因子：
3.2
作者：
Hatva, E;Jaaskelainen, J;Haltia, M
通讯作者：
Haltia, M