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LncRNA XLOC235与RP11-789经由smad4“对话”进而协同介导胃癌转移的 研究
结题报告
批准号:
81871908
项目类别:
面上项目
资助金额:
54.0 万元
负责人:
宋武
依托单位:
学科分类:
H1808.肿瘤微环境
结题年份:
2022
批准年份:
2018
项目状态:
已结题
项目参与者:
陈冬良、曹清华、李广华、陈泽宏、周志军、王小群、巫家霖
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中文摘要
转移是影响胃癌患者预后的最重要因素。研究表明长链非编码RNA(lncRNA)与胃癌转移密切相关,目前对lncRNA与胃癌转移的相关机制挖掘不足,更鲜有研究关注多个lncRNAs的协同影响。项目组首次从胃癌淋巴转移标本中筛选出两个lncRNA XLOC235和RP11-789,并证实二者对胃癌转移有重要影响,但其是否协同介导胃癌转移及具体分子机制尚不清楚。项目组发现二者均与smad4特定序列存在结合位点,提出两个lncRNA间存在缠绕绑定的“对话”机制,特异影响smad4转录并经Wnt信号通路协同介导胃癌转移的科学假设,拟利用体内外模型系统探讨XLOC235与RP11-789经smad4实现的“对话”作用模式和协同影响的信号通路变化对胃癌转移治疗的价值。此研究有利于阐明XLOC235和RP11-789协同影响胃癌转移的关键机制,为利用靶向lncRNA诊断和治疗胃癌转移提供更充分的科学依据。
英文摘要
Metastasis is the most important factor affecting the prognosis of patients with gastric cancer. Studies had shown that long non-coding RNAs(lncRNAs) were closely associated with metastasis of gastric cancer. However, the exploration of the molecular mechanism regarding the relation between lncRNAs and gastric cancer metastasis is insufficient, and there are few researches focusing on the synergistic effect of multiple lncRNAs. Our research group for the first time identified two lncRNAs, XLOC235 and RP11-789, from the metastasized lymph node specimens of gastric cancer. We further confirmed that they had important effects on gastric cancer metastasis. Yet whether these two lncRNAs could collaboratively mediate metastasis in gastric cancer and its specific molecular mechanisms remain unclear. We also found that both of these lncRNAs had binding sites to the specific sequences of smad4. On this basis, our group puts forward a hypothesis that there is a tangling "crosstalk" mechanism between lncRNA XLOC235 and RP11-789, which specifically influences transcription of smad4 and further mediates the invasion and metastasis of gastric cancer through WNT signaling pathway. In vitro and in vivo models will be used to systematically investigate the "crosstalk" mechanism of XLOC235 and RP11-789 , its synergistic effects to the WNT signaling pathways by smad4 and the significance for the treatment of gastric cancer metastasis. This study will help us understand the key mechanism of lncRNA XLOC235 and rp11-789 collaboratively influencing the metastasis of gastric cancer, providing a better scientific evidence of using lncRNAs as targeted therapy for the diagnosis and treatment for gastric cancer metastasis.
胃癌转移是影响其预后的重要因素,胃癌侵袭转移的分子机制及影响因素尚未明确。前期研究发现 lncRNA XLOC235可调控胃癌细胞的侵袭迁移能力,上调/下调lncRNA RP11-789显著改变胃癌细胞侵袭迁移能力,EMT通路是胃癌侵袭转移过程中最重要的通路之一。lncRNA XLOC235与lncRNA RP11-789都可以调节EMT通路并调控SMAD4,而据此项目组提出lncRNA XLOC235与lncRNA RP11-789通过smad4协同调控EMT影响胃癌转移。课题组建立lncRNA XLOC235与lncRNA RP11-789上/下调的体内外实验模型;阐释lncRNA XLOC235与lncRNA RP11-789通过smad4调控EMT影响肿瘤的转移,同时多组学测序,通过蛋白-miRNA-lncRNA调节网络的进一步理解lncRNAXLOC235与lncRNARP11-789互作分子基础,以 lncRNA XLOC235与lncRNA RP11-789为新靶点探索预防胃癌侵袭转移新策略,阐明lncRNA影响肿瘤侵袭性和转移性的作用机理。
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
Integrated analysis of the functions and clinical implications of exosome circRNAs in colorectal cancer.
外泌体circRNA在结直肠癌中的功能和临床意义的综合分析
DOI:10.3389/fimmu.2022.919014
发表时间:2022
期刊:Frontiers in immunology
影响因子:7.3
作者:
通讯作者:
A Prognostic Model Using Immune-Related Genes for Colorectal Cancer.
使用免疫相关基因治疗结直肠癌的预后模型
DOI:10.3389/fcell.2022.813043
发表时间:2022
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Feng W;Zhang Y;Liu W;Wang X;Lei T;Yuan Y;Chen Z;Song W
通讯作者:Song W
A Diagnostic Model Using Exosomal Genes for Colorectal Cancer.
使用外泌体基因诊断结直肠癌的模型
DOI:10.3389/fgene.2022.863747
发表时间:2022
期刊:Frontiers in genetics
影响因子:3.7
作者:
通讯作者:
Identification of 14 Differentially-Expressed Metabolism-Related Genes as Potential Targets of Gastric Cancer by Integrated Proteomics and Transcriptomics.
综合蛋白质组学和转录组学鉴定 14 个差异表达的代谢相关基因作为胃癌的潜在靶点
DOI:10.3389/fcell.2022.816249
发表时间:2022
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Zhang Y;Liu W;Feng W;Wang X;Lei T;Chen Z;Song W
通讯作者:Song W
整合素β5调控TGFβ II型受体细胞内转 运促进胃癌转移的机制研究
  • 批准号:
    --
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2025
  • 负责人:
    宋武
  • 依托单位:
HOXB13与Meis1协同调控骶神经嵴细胞迁移分化及其在先天性巨结肠中作用机制研究
  • 批准号:
    --
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2021
  • 负责人:
    宋武
  • 依托单位:
国内基金
海外基金