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.
