RFX5诱导的lncRNA LOC101928222下调NKG2D/MICA促进结直肠癌细胞免疫逃逸的机制研究

批准号:
81972278
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
王科明
依托单位:
学科分类:
肿瘤免疫治疗
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王科明
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中文摘要
恶性肿瘤能逃避机体免疫防线的围剿,免疫微环境在肿瘤免疫逃逸中起着主要作用。本课题组分析GEO数据库发现在结直肠癌(CRC)患者癌组织中LOC101928222异常高表达,预试验发现LOC101928222下调CRC细胞表面MICA,并通过TGF-β下调NK细胞表面NKG2D,抑制MICA与NKG2D结合,从而削弱NK细胞识别和杀伤CRC细胞的功能。据此提出假设:LOC101928222通过招募EZH2和DNMT1在转录水平下调MICA,同时竞争性结合miR-625-5p在转录后水平上调TGF-β,进而下调NK细胞表面NKG2D,抑制NK细胞的识别和杀伤功能,促进CRC细胞免疫逃逸。课题组将利用临床组织标本及动物模型验证上述假设,在细胞水平应用相关技术探究其机制。本课题旨在运用数据分析和生命科学领域中的前沿理论及方法,为CRC的免疫治疗及免疫逃逸机制提供新的实验研究基础和理论依据。
英文摘要
Immune microenvironment plays a major role in tumor immune evasion so that the tumor could escape the annihilates of the immune defense. In our previous study, we firstly analyzed the GEO database and found that the abnormal high expression of LOC101928222 in CRC patients' cancer tissues . The high experssion LOC101928222 could down-regulated the experssion of MICA on the surface of colorectal cancer cells and the experssion of NKG2D on the surface of NK cell by upregulating the experssion of TGF-β. Then, LOC101928222 could weaken the ability of NK cells to recognize and kill CRC cells by inhibiting the binding of MICA to NKG2D . So we hypothesized that LOC101928222 could down-regulate the experssion of MICA at the transcriptional level by recruiting EZH2 and DNMT1, meanwhile, down-regulate the experssion of NKG2D on the surface of NK cells by up-regulating the experssion of TGF-β at the post-transcriptional level through competing with miR-625-5p, and further inhibiting the recognition and killing function of NK cells and promoting the immune escape of CRC cells. We will use clinical tissue specimens and animal models to verify the hypothesis, and apply relevant techniques at the cellular level to explore its mechanism. This study aims to provide a new experimental research and theoretical basis for the immunotherapy and immune evasion mechanism of CRC by using the frontier theory and methods in data analysis and life sciences.
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DOI:10.1080/21655979.2022.2074666
发表时间:2022-05
期刊:Bioengineered
影响因子:4.9
作者:
通讯作者:
DOI:10.3390/cells11193008
发表时间:2022-09-27
期刊:Cells
影响因子:6
作者:
通讯作者:
LncRNA SH3PXD2A-AS1介导溃疡性结肠炎“炎-癌”转变的作用及 机制研究
- 批准号:81772603
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2017
- 负责人:王科明
- 依托单位:
国内基金
海外基金
