课题基金基金详情
核糖体蛋白L3在神经纤维瘤中靶向NF1的作用及机制研究
结题报告
批准号:
62003107
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王元丽
依托单位:
学科分类:
生物、医学信息系统与技术
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王元丽
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中文摘要
NF1基因突变或抑制异常导致Ras信号通路的过度活化,最终引起神经纤维瘤(NF)的发生。目前主要运用Ras通路相关信号因子的抑制剂来治疗NF,但疗效仅局限于抑制细胞的生长,一旦停止用药肿瘤便迅速再生,并且长期单靶点用药极易产生耐药性,因此迫切需要开发新的抗肿瘤药物。前期研究,采用CRISPR构建NF1果蝇突变细胞系,并结合RNAi筛选获得肿瘤多个候选靶基因,预实验结果表明核糖体蛋白L3(RPL3)可能与NF1基因具有合成致死作用(Synthetic lethality)。本项目拟在前期研究的基础上,采用RNAi、Western Blot、流式细胞检测技术和免疫共沉淀等分子手段,研究RPL3靶向NF1在神经纤维瘤中的功能及作用机理,探讨RPL3在Ras信号通路的分子调节机制,以期阐明神经纤维瘤的发病机制,为帮助开发新的抗癌药物和多靶点治疗神经纤维瘤提供理论基础和科学依据。
英文摘要
Mutation or aberrant inhibition of NF1 leads to overexpression of Ras, eventually causing neurofibromatosis. Current therapeutic strategies is mainly treated with inhibitors of Ras pathway and related signaling factors. However, such treatments are limited to cytostatic effects, and tumors rapidly regrow after cessation of treatment, and it's easier to become drug-resistant for long-term single target treatment. Therefore, there is an urgent need to identify novel drugs to treat neurofibromatosis. Our previous study identified some of candidate gene targets for neurofibromatosis in synthetic screens using NF1 Drosophila mutant cell lines by CRISPR, combining RNAi. The preliminary data indicated that the ribosomal protein L3(RPL3)may have synthetic lethality effect with NF1 gene. On the basis of previous studies, this project intends to use the molecular technology of RNAi, Western Blot, flow cytometry and immunoprecipitation to study the function and molecular mechanisms of targeting NF1 by RPL3 in neurofibromatosis. We will further investigate the molecular mechanisms of RPL3 in the Ras signaling pathway. The project will elucidate the pathogenesis of neurofibromatosis, and provide the theoretical grounds and scientific basis for the development of new anticancer drugs and multi-target treatment of neurofibromatosis.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.3389/fmed.2023.1321515
发表时间:2023
期刊:FRONTIERS IN MEDICINE
影响因子:3.9
作者:Deng, Zhenfeng;Li, Chunhong;Wang, Yingjin;Wu, Fengwen;Liang, Chunfang;Deng, Wei;Wang, Yuanli
通讯作者:Wang, Yuanli
DOI:10.3390/cells11223587
发表时间:2022-11-13
期刊:Cells
影响因子:6
作者:
通讯作者:
DOI:10.1111/cge.13998
发表时间:2021
期刊:Clinical Genetics
影响因子:--
作者:Yuanli Wang;Dawu Zheng
通讯作者:Dawu Zheng
Metagenomic next-generation sequencing contributes to the diagnosis of mixed pulmonary infection: a case report.
宏基因组下一代测序有助于诊断混合肺部感染:病例报告。
DOI:10.1186/s12941-022-00545-z
发表时间:2022-11-24
期刊:ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
影响因子:5.7
作者:Qin, Ziqian;Zou, Yiwu;Huang, Zehe;Yu, Ning;Deng, Zhenfeng;Chen, Zhencheng;Wang, Yuanli
通讯作者:Wang, Yuanli
DOI:10.1021/acs.langmuir.1c03286
发表时间:2022-03
期刊:Langmuir : the ACS journal of surfaces and colloids
影响因子:--
作者:Yao Wang;Yuanli Wang;F. Hu;Lizhen Zeng;Zhencheng Chen;Mingzhu Jiang;Shangjun Lin;Weisi Guo;Dongxia Li
通讯作者:Yao Wang;Yuanli Wang;F. Hu;Lizhen Zeng;Zhencheng Chen;Mingzhu Jiang;Shangjun Lin;Weisi Guo;Dongxia Li
国内基金
海外基金