葡萄膜黑色素瘤OUM1靶向PTPRZ1调控蛋白酪氨酸磷酸酶活性的机制研究
结题报告
批准号:
81972524
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
张蕾蕾
依托单位:
学科分类:
基于特殊临床特征的肿瘤研究
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
张蕾蕾
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中文摘要
葡萄膜黑色素瘤(Uveal Melanoma,UM)是成人最常见的眼内恶性肿瘤,易复发转移,致死率高。前期研究发现:1、UM中多条长非编码RNA(lncRNA)异常高表达,其中新发现的位于UM细胞质中的lncRNA OUM1明显上调。2、敲除UM细胞质中OUM1表达显著抑制PTPs活性及细胞增殖和侵袭转移;3、分子生物学实验和生物信息学证实蛋白酪氨酸磷酸酶受体Z1(PTPRZ1)是OUM1的下游靶基因,参与UM侵袭转移;据此推测:UM细胞质中异常高表达的OUM1通过靶向上调PTPRZ1表达,增强PTPs活性进而促进UM细胞侵袭转移。本研究将借助UM细胞系,采用寡核苷酸沉淀(CHOP)和RNA染色体构象捕获(R3C)等技术筛选并检测OUM1调控PTPRZ1表达的作用机制,以期揭示OUM1增强PTPs活性促进UM侵袭转移的作用机制,为UM患者临床治疗提供理论依据和潜在治疗靶点。
英文摘要
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults with high death rate because of the high relapse and metastasis rate. Preliminary study found: 1.Various of long non-coding RNAs (lncRNAs) are over-expressed in UM and the newly discovered lncRNA OUM1 over-expressed significantly; lncRNA OUM1 located in the cytoplasm of UM cells. 2.Knockdown of OUM1 expression could significantly inhibited PTPs activity, cell proliferation, invasion and metastasis. 3.Biological experiments and bioinformatics confirmed that PTPRZ1 is the downstream target gene of OUM1, which is involved in the proliferation and metastasis of UM. Above all, it is speculated that the abnormally up-regulated OUM1 could enhance the activity of PTPs by targeting up-regulation of PTPRZ1 expression, which lead to the invasion and metastasis of UM cells. This study will use the UM cell lines to study the mechanism of OUM1 enhancing PTPs activity and promoting invasion and metastasis of UM. Oligonucleotide precipitation (CHOP) and RNA chromosome conformation capture (R3C) techniques will be used to screen and detect the mechanism of OUM1 regulating PTPRZ1 expression, so as to reveal the molecular biological mechanism of lncRNA OUM1 in PTPs activity and UM proliferation and metastasis. Finally, this will provide theoretical basis and potential therapeutic targets for clinical treatment of UM patients.
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专利列表
DOI:10.3389/fbioe.2020.579439
发表时间:2020
期刊:Frontiers in bioengineering and biotechnology
影响因子:5.7
作者:Zhang L;Pan H;Li Y;Li F;Huang X
通讯作者:Huang X
DOI:10.3389/fonc.2020.00325
发表时间:2020-04
期刊:Frontiers in Oncology
影响因子:4.7
作者:Leilei Zhang;Xiaolin Huang;Tao Guo;Huixue Wang;Haiyan Fan;Li Fang
通讯作者:Leilei Zhang;Xiaolin Huang;Tao Guo;Huixue Wang;Haiyan Fan;Li Fang
DOI:10.1186/s12886-020-01587-7
发表时间:2020-08-03
期刊:BMC OPHTHALMOLOGY
影响因子:2
作者:Li, Fang;Zhang, Leilei;Zhu, Dongqing
通讯作者:Zhu, Dongqing
DOI:10.3389/fgene.2022.834111
发表时间:2022
期刊:Frontiers in genetics
影响因子:3.7
作者:Li Y;Liu X;Zhang W;Song X;Zhang L;Xiao C
通讯作者:Xiao C
DOI:10.1016/j.jcjo.2021.07.007
发表时间:2021
期刊:Canadian journal of ophthalmology. Journal canadien d'ophtalmologie
影响因子:--
作者:Weiwei Tang;Leilei Zhang;Zhengkang Li;Yuan Deng
通讯作者:Yuan Deng
长非编码LINC00622调控UM增殖和侵袭转移的机制研究
  • 批准号:
    81602366
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    18.0万元
  • 批准年份:
    2016
  • 负责人:
    张蕾蕾
  • 依托单位:
国内基金
海外基金