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SHP2 介导胃癌细胞中 ROS/JNK/NFAT4 信号通路促使 lncRNA SNHG18 经 CAR-T 细胞驱动胃癌生长与转移

英文原题:SHP2 mediates the ROS/JNK/NFAT4 signaling pathway in gastric cancer cells prompting lncRNA SNHG18 to drive gastric cancer growth and metastasis via CAR-T cells.

查看英文原题

SHP2 mediates the ROS/JNK/NFAT4 signaling pathway in gastric cancer cells prompting lncRNA SNHG18 to drive gastric cancer growth and metastasis via CAR-T cells.

PubMed 2024/07/06(内容时间) Heliyon

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研究思路按摘要原文分段

在胃癌细胞中,CAR-T 细胞的影响可在抑制胃癌进展的过程中产生,本研究可探讨酪氨酸磷酸酶SHP2的作用及其分子机制。

研究利用裸鼠皮下肿瘤模型评估胃癌进展。采用Western blotting检测蛋白表达,同时通过Q-PCR检测MGC-803细胞中lncRNA SNHG18和miR-211-5p的表达水平。miR-211-5p与lncRNA SNHG18之间的关系可通过双荧光素酶报告基因进行分析。通过划痕愈合和transwell实验测定MGC-803细胞的迁移能力,并使用CCK-8实验评估细胞增殖。

发现SHP2抑制CAR-T 细胞对MGC-803细胞的细胞毒性作用,并抑制MGC-803细胞中ROS/JNK/NFAT4信号通路相关蛋白的表达以及CAR-T 细胞中miR-211-5p/BRD4轴。此外,MGC-803细胞的增殖、侵袭和迁移受到促进,而miR-211-5p的表达可被ncRNA SNHG18特异性抑制,如下所示:胃癌细胞中的SHP2介导ROS/JNK/NFAT4信号通路并诱导lncRNA SNHG18,后者通过CAR-T 细胞中的miR-211-5p/BRD4轴促进胃癌生长和转移。

展开英文摘要原文

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.

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.

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.

论文信息

作者
An L、Huo Y、Xiao N、Su S、Wang K
单位
Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei, 071000, PR China.China
期刊
Heliyon2024 Jul 30
原文标识
PubMed 39130478 · DOI 10.1016/j.heliyon.2024.e34008