外泌体转运的长链非编码RNA HIF1A-AS2作为ceRNA调控结肠癌有氧糖酵解和转移的分子机制研究

批准号:
81972293
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
李大卫
依托单位:
学科分类:
肿瘤表观遗传
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
李大卫
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中文摘要
肿瘤细胞分泌的外泌体含有lncRNA等多种生物活性物质,通过介导细胞间的信号传递,广泛参与了肿瘤发生、转移和肿瘤微环境调控。具体机制有待阐明。我们前期通过对结肠癌正常黏膜-原发癌-肝转移癌进行高通量差异筛选和后续功能学验证,首次发现:(一)lncRNA HIF1A-AS2是调控结肠癌有氧糖酵解和转移的潜在靶点;(二)HIF1A-AS2可通过吸附miRNA,减少后者对己糖激酶HK1和FoxC1 mRNA的降解,上调HK1和FoxC1蛋白水平;(三) hnRNPA2B1蛋白能够介导HIF1A-AS2以外泌体形式转运,促进受体肿瘤细胞的有氧糖酵解能力和转移。本研究拟通过体内外实验,揭示HIF1A-AS2外泌体的转运机制,以及调控结肠癌糖酵解和转移的作用机制,最终为结肠癌诊治提供关键的分子标记和干预靶点。
英文摘要
Exosomes secreted by tumor cells contain a variety of biologically active substances such as lncRNA, which are widely involved in tumorigenesis, metastasis, and tumor microenvironment regulation by mediating signal transmission between cells. The specific mechanism has yet to be clarified. We have previously screened for high-throughput differences in normal mucosal-primary cancer-liver metastases of colon cancer. Through subsequent functional verification,we first discovered, (1) lncRNA HIF1A-AS2 is a potential target for regulating aerobic glycolysis and metastasis of colon cancer;(2) HIF1A-AS2 can reduce the degradation of hexokinase HK1 and FoxC1 mRNA and up-regulate HK1 and FoxC1 protein levels by sponge miRNA;(3) The hnRNPA2B1 protein mediates HIF1A-AS2 exosomal transport and promotes aerobic glycolysis and metastasis of recipient tumor cells. This study intends to reveal the transport mechanism of HIF1A-AS2 into exosomes and the mechanism of regulation of glycolysis and metastasis of colon cancer through in vitro and in vivo experiments, and finally provide key molecular markers and intervention targets for the diagnosis and treatment of colon cancer.
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
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine
Cul4A-DDB1介导的磷酸甘油酸脱氢酶单泛素化通过增加S-腺苷甲硫氨酸促进结直肠癌转移
DOI:10.1172/jci146187
发表时间:2021-11-01
期刊:JOURNAL OF CLINICAL INVESTIGATION
影响因子:15.9
作者:Zhang, Yajuan;Yu, Hua;Yang, Weiwei
通讯作者:Yang, Weiwei
RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA.
RNA结合蛋白IMP3是MEK1/ERK信号通路的新型调节剂,通过稳定MEKK1 mRNA来调节结直肠癌的进展
DOI:10.1186/s13046-021-01994-8
发表时间:2021-06-21
期刊:Journal of experimental & clinical cancer research : CR
影响因子:--
作者:Zhang M;Zhao S;Tan C;Gu Y;He X;Du X;Li D;Wei P
通讯作者:Wei P
DOI:10.1002/ctm2.1352
发表时间:2023-08
期刊:Clinical and translational medicine
影响因子:10.6
作者:
通讯作者:
Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer.
肿瘤源性外泌体miR-934诱导巨噬细胞M2极化促进结直肠癌肝转移
DOI:10.1186/s13045-020-00991-2
发表时间:2020-11-19
期刊:Journal of hematology & oncology
影响因子:28.5
作者:Zhao S;Mi Y;Guan B;Zheng B;Wei P;Gu Y;Zhang Z;Cai S;Xu Y;Li X;He X;Zhong X;Li G;Chen Z;Li D
通讯作者:Li D
DOI:10.1155/2022/9935705
发表时间:2022
期刊:JOURNAL OF IMMUNOLOGY RESEARCH
影响因子:4.1
作者:Zhong, Xinyang;He, Xuefeng;Wang, Yaxian;Hu, Zijuan;Yu, Deshui;Huang, Huixia;Zhao, Senlin;Wei, Ping;Li, Dawei
通讯作者:Li, Dawei
JPH3调控糖酵解和肿瘤干细胞干性参与结肠癌进展的作用机制研究
- 批准号:81772583
- 项目类别:面上项目
- 资助金额:57.0万元
- 批准年份:2017
- 负责人:李大卫
- 依托单位:
IMP3调控上皮间质转化和肿瘤干细胞进而参与结肠癌发生和转移的机制研究
- 批准号:81472222
- 项目类别:面上项目
- 资助金额:72.0万元
- 批准年份:2014
- 负责人:李大卫
- 依托单位:
癌转移促进基因IMP3在结肠癌中的功能和相关信号通路的机制研究
- 批准号:81101586
- 项目类别:青年科学基金项目
- 资助金额:22.0万元
- 批准年份:2011
- 负责人:李大卫
- 依托单位:
国内基金
海外基金
