微环境MSC异常表达miR-374-5p促进胃炎/癌转化的作用及机制研究
结题报告
批准号:
81702429
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
纪润璧
依托单位:
学科分类:
H1802.肿瘤发生
结题年份:
2020
批准年份:
2017
项目状态:
已结题
项目参与者:
祝源、韩月、赵文君、唐浩、张淡宜、徐雪莹、张鹏
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中文摘要
炎/癌微环境与胃癌发生发展密切相关,MSC是炎/癌微环境的重要组成部分。我们发现与癌旁组织MSC(GCN-MSC)相比,胃癌组织MSC(GC-MSC)显著促进胃癌细胞生长和转移;GC-MSC及其exosome中miR-374-5p表达上调;miR-374-5p调控MSC表型和功能;大鼠胃炎组织MSC可诱导胃上皮细胞恶性转化。微环境MSC高表达miR-374-5p参与胃炎/癌转化的作用及机制不清楚。因此,本课题拟以胃组织来源MSC为研究对象,比较炎/癌微环境中MSC生物学表型和促炎/癌转化功能的差异;明确MSC通过miR-374-5p推动胃炎/癌转化的机制;鉴定miR-374-5p下游靶基因及信号转导通路;并在构建的大鼠胃炎/癌转化模型中进行验证。本研究将为阐明MSC在胃癌发生发展中的作用提供新的理论依据,同时也为胃癌诊疗提供新的靶点,具有重要的科学价值和临床意义。
英文摘要
The initiation and progression of gastric cancer is closely associated with inflammatory and cancer microenvironment. We found that compared to MSC from human normal control tissues (GCN-MSC), MSC from gastric cancer tissues (GC-MSC) had more profound tumor-promoting role. GC-MSC and its exosome expressed higher levels of miR-374-5p and confirmed that miR-374-5p could regulate the phenotype and function of MSC. We also isolated MSC from the gastric tissues of rats with gastritis and found that they have the capacity of promoting the malignant transformation of gastric epithelial cells. The roles and mechanisms of microenvironment-resident MSC-mediated malignant transformation from gastritis to gastric cancer with higher expression of miR-374-5p were unknown. Thus, in this study, we will compare the phenotypes and functions of the MSC from different gastric tissues in promoting malignant transformation from gastritis to gastric cancer; clarify the role of miR-374-5p in the regulation of MSC involved in the malignant transformation. The target genes and downstream signaling pathways of miR-374-5p will be further studied. The promoting roles of MSC in the malignant transformation from gastritis to gastric cancer will be confirmed in a rat model. The proposed study will help understand the roles and mechanisms of MSC in the initiation and progression of gastric cancer and provide novel targets for the diagnosis and therapy of gastric cancer, which has important scientific value and clinical significance.
该项目以临床胃炎、胃癌和癌旁组织来源MSC为切入点,阐述了胃炎和胃癌微环境中MSC表型和功能的差异,探索了MSC高表达miR-374-5p促进胃癌增殖、迁移和耐药的作用于机制。研究表明miR-374-5p不仅能够调控MSC表型特征,促进MSC增殖、迁移和炎症因子分泌;还可调控MSC功能,通过有效的生物活性物质(如外泌体)发挥促进胃癌细胞增殖、迁移和耐药等作用。通过研究miR-374-5p作用机制,鉴定出3个下游靶点:Neurod1,HAPLN1和Wnt5a,为临床后续研究提供理论基础。在临床应用探索方面,发现miR-374-5p表达水平在癌前病变、胃癌和复发患者血清中升高,而在胃癌术后患者血清中降低,提示其为潜在的胃癌诊断和预后判断指标。发表论文7篇,其中SCI论文4篇,单篇最高IF: 7.032。
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:10.13312/j.issn.1671-7783.y180131
发表时间:2018
期刊:江苏大学学报(医学版)
影响因子:--
作者:纪润璧;顾红兵
通讯作者:顾红兵
Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity
胃癌细胞的细胞外囊泡诱导中性粒细胞表达 PD-L1,从而抑制 T 细胞免疫
DOI:10.3389/fonc.2020.00629
发表时间:2020-05-13
期刊:FRONTIERS IN ONCOLOGY
影响因子:4.7
作者:Shi, Yinghong;Zhang, Jiahui;Zhang, Xu
通讯作者:Zhang, Xu
Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis
胃癌来源的间充质干细胞:白藜芦醇抑制胃癌转移的一个有前景的靶点
DOI:10.1007/s13577-020-00339-5
发表时间:2020-04-29
期刊:HUMAN CELL
影响因子:4.3
作者:Yin, Lei;Zhang, Rongxue;Qian, Hui
通讯作者:Qian, Hui
DOI:--
发表时间:2018
期刊:中国实验动物学报
影响因子:--
作者:纪润璧;马吉春;闻向梅;林江
通讯作者:林江
DOI:--
发表时间:2018
期刊:American Journal of Translational Research
影响因子:2.2
作者:Sun Zixuan;Chen Jingyan;Zhang Jiao;Ji Runbi;Xu Wenrong;Zhang Xu;Qian Hui
通讯作者:Qian Hui
国内基金
海外基金