ZNF750靶向调控VEGF-C/VEGFR-3抑制食管鳞癌淋巴管生成及淋巴结转移的作用机制研究
结题报告
批准号:
82002606
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
毕炀辉
依托单位:
学科分类:
肿瘤复发与转移
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
毕炀辉
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中文摘要
食管癌是我国第三大肿瘤,组织学类型以食管鳞癌为主,由于淋巴结清除的局限性和微转移的存在,易复发转移,预后极差。前期研究发现ZNF750 在ESCC组织中存在显著失活突变及拷贝数缺失,与ESCC淋巴结转移及预后相关,且野生型ZNF750能抑制ESCC细胞侵袭迁移、血管及淋巴管生成。ChIP实验发现,ZNF750可以结合淋巴管生成相关生长因子VEGF-C的启动子区调控其表达,提示ZNF750可能通过调控VEGF-C/VEGFR-3抑制ESCC的淋巴管生成及淋巴结转移。本项目拟采用双荧光素酶报告基因实验、挽救实验、transwell 共培养系统和裸鼠腘窝淋巴结转移模型等明确ZNF750通过VEGF-C/VEGFR-3发挥抑制ESCC淋巴管生成及淋巴结转移的作用及机制;同时收集临床病例探讨ZNF750蛋白在ESCC淋巴管生成及淋巴结转移中的应用效果,为ESCC的分子靶向及个体化治疗提供依据。
英文摘要
Esophageal carcinoma was the third most common cancer in China and the main histological type is esophageal squamous cell carcinoma. The limitation of lymph node clearance and the presence of micrometastases lead to the recurrence and metastasis of cancers and a poor prognosis of ESCC. Our previous study showed that ZNF750 harbored significant inactivating mutations and obviously copy number deletions, which are related to lymph node metastasis and prognosis of ESCC. And ZNF750 can inhibit the metastasis,angiogenesis and lymphangiogenesis of ESCC cell lines. ChIP experiment showed that ZNF750 combined the VEGF-C promoter and regulated the expression of VEGF-C. These results suggested ZNF750 inhibited lymphangiogenesis and lymph node metastasis of ESCC through regulating VEGF-C/VEGFR-3 pathway. This proposal aims to reveal the effect and molecular mechanism of ZNF750 on lymphangiogenesis and lyphm node metastasis of ESCC by dual-luciferase reporter assay, rescue experiment, transwell co-culture system and popliteal lymph node metastasis nude mouse model. In addition, we will collect clinical cases to claclafy the effect of ZNF750 protein on lymphangiogenesis and lymph node metastasis of ESCC, and provide a basis for molecular targeted therapy and individualized treatment of ESCC.
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DOI:10.4149/neo_2023_230104n8
发表时间:2023-11
期刊:Neoplasma
影响因子:3
作者:Y. Bi;Yanfang Yang;Yong Zhang;Caixia Cheng;Peisen Tang;Heng Xiao;Fajia Yuan;Weiwei Wu
通讯作者:Y. Bi;Yanfang Yang;Yong Zhang;Caixia Cheng;Peisen Tang;Heng Xiao;Fajia Yuan;Weiwei Wu
DOI:10.1016/j.isci.2024.108833
发表时间:2024-02-16
期刊:ISCIENCE
影响因子:5.8
作者:Bi,Yanghui;Chen,Jieya;Zhang,Ruiping
通讯作者:Zhang,Ruiping
国内基金
海外基金