PDF(Pubmed)
Abstract：
OBJECTIVE: In gastric cancer cells, the influence of CAR T cells can be produced in the process of inhibiting the progression of gastric cancer, and the role of tyrosine phosphatase SHP2 can be explored in this study, along with its molecular mechanisms.
METHODS: The research utilized subcutaneous tumor models in nude mice to assess gastric cancer progression. Protein expression was detected using Western blotting, while Q-PCR examined the expression levels of lncRNA SNHG18 and miR-211-5p in MGC-803 cells. The relationship between miR-211-5p and lncRNA SNHG18 can be analyzed by dual luciferase reporter genes. The migratory ability of MGC-803 cells was determined through wound healing and transwell experiments, and cell proliferation was evaluated using a CCK-8 assay.
RESULTS: SHP2 was found to inhibit the cytotoxic effects of CAR-T cells on MGC-803 cells, and it suppressed the expression of proteins related to the ROS/JNK/NFAT4 signaling pathway in MGC-803 cells and the miR-211-5p/BRD4 axis in CAR-T cells. In addition, the proliferation, invasion and migration of MGC-803 cells were promoted, and the expression of miR-211-5p could be inhibited specifically by ncRNA SNHG18, as shown below:SHP2 in gastric cancer cells mediates the ROS/JNK/NFAT4 signaling pathway and induces lncRNA SNHG18, which, through the miR-211-5p/BRD4 axis in CAR-T cells, promotes gastric cancer growth and metastasis.
METHODS: The research utilized subcutaneous tumor models in nude mice to assess gastric cancer progression. Protein expression was detected using Western blotting, while Q-PCR examined the expression levels of lncRNA SNHG18 and miR-211-5p in MGC-803 cells. The relationship between miR-211-5p and lncRNA SNHG18 can be analyzed by dual luciferase reporter genes. The migratory ability of MGC-803 cells was determined through wound healing and transwell experiments, and cell proliferation was evaluated using a CCK-8 assay.
RESULTS: SHP2 was found to inhibit the cytotoxic effects of CAR-T cells on MGC-803 cells, and it suppressed the expression of proteins related to the ROS/JNK/NFAT4 signaling pathway in MGC-803 cells and the miR-211-5p/BRD4 axis in CAR-T cells. In addition, the proliferation, invasion and migration of MGC-803 cells were promoted, and the expression of miR-211-5p could be inhibited specifically by ncRNA SNHG18, as shown below:SHP2 in gastric cancer cells mediates the ROS/JNK/NFAT4 signaling pathway and induces lncRNA SNHG18, which, through the miR-211-5p/BRD4 axis in CAR-T cells, promotes gastric cancer growth and metastasis.
摘要：
目的：在胃癌细胞中，在抑制胃癌进展的过程中可以产生CAR-T细胞的影响,酪氨酸磷酸酶SHP2的作用可以在这项研究中探索，以及它的分子机制。
方法：本研究利用裸鼠皮下肿瘤模型评估胃癌进展。蛋白质表达检测使用蛋白质印迹,而Q-PCR检测了MGC-803细胞中lncRNASNHG18和miR-211-5p的表达水平。miR-211-5p和lncRNASNHG18之间的关系可以通过双荧光素酶报告基因分析。通过伤口愈合和transwell实验确定MGC-803细胞的迁移能力，使用CCK-8测定评估细胞增殖。
结果：SHP2被发现抑制CAR-T细胞对MGC-803细胞的细胞毒作用，抑制MGC-803细胞中ROS/JNK/NFAT4信号通路相关蛋白的表达和CAR-T细胞中miR-211-5p/BRD4轴的表达。此外,扩散,促进MGC-803细胞的侵袭和迁移，miR-211-5p的表达可以被ncRNASNHG18特异性抑制,如下所示:SHP2在胃癌细胞中介导ROS/JNK/NFAT4信号通路,通过CAR-T细胞中的miR-211-5p/BRD4轴，促进胃癌的生长和转移。
方法：本研究利用裸鼠皮下肿瘤模型评估胃癌进展。蛋白质表达检测使用蛋白质印迹,而Q-PCR检测了MGC-803细胞中lncRNASNHG18和miR-211-5p的表达水平。miR-211-5p和lncRNASNHG18之间的关系可以通过双荧光素酶报告基因分析。通过伤口愈合和transwell实验确定MGC-803细胞的迁移能力，使用CCK-8测定评估细胞增殖。
结果：SHP2被发现抑制CAR-T细胞对MGC-803细胞的细胞毒作用，抑制MGC-803细胞中ROS/JNK/NFAT4信号通路相关蛋白的表达和CAR-T细胞中miR-211-5p/BRD4轴的表达。此外,扩散,促进MGC-803细胞的侵袭和迁移，miR-211-5p的表达可以被ncRNASNHG18特异性抑制,如下所示:SHP2在胃癌细胞中介导ROS/JNK/NFAT4信号通路,通过CAR-T细胞中的miR-211-5p/BRD4轴，促进胃癌的生长和转移。
