引用本文:黄珊珮,韦二丹,朱丽叶,宁绮婷,陈形梅,陈 妮,吴江妮,丘新泽,黄杰安,刘诗权.FTO、GSDMD在胃癌组织中的表达及其作用机制研究[J].中国临床新医学,2024,17(4):400-406.
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FTO、GSDMD在胃癌组织中的表达及其作用机制研究
黄珊珮,韦二丹,朱丽叶,宁绮婷,陈形梅,陈 妮,吴江妮,丘新泽,黄杰安,刘诗权
广西医科大学第二附属医院消化内科,南宁 530007
摘要:
[摘要] 目的 探讨肥胖相关蛋白(FTO)与消皮素D(GSDMD)在胃癌(GC)组织中的表达及其作用机制。方法 通过TIMER 2.0数据库分析FTO及GSDMD在GC组织中的差异表达。收集2022年1月至2023年3月广西医科大学第二附属医院手术切取的GC组织及其对应癌旁组织(距离肿瘤边缘3~5 cm)各45例,并收集患者的临床病理资料。采用免疫组织化学染色法检测组织中FTO、GSDMD的表达情况,分析其与患者临床病理特征的关联性。通过转染低表达FTO慢病毒构建低表达FTO的AGS细胞(FTO低表达组),并以转染空载体慢病毒的细胞作为对照组。采用实时荧光定量聚合酶链式反应(RT-PCR)法检测两组细胞FTO mRNA、GSDMD mRNA的表达水平;采用细胞划痕实验及细胞迁移实验分析两组细胞迁移能力。结果 基于TIMER 2.0数据库的分析结果及免疫组织化学染色结果显示,FTO、GSDMD在GC组织中呈高表达(P<0.05)。FTO和GSDMD高表达均与肿瘤侵犯深度、淋巴结转移密切相关(P<0.05)。细胞实验结果显示,FTO低表达组的GSDMD mRNA表达水平显著低于对照组(P<0.05),划痕愈合率更低,细胞迁移数更少,差异均有统计学意义(P<0.05)。结论 FTO可能通过调控GSDMD表达促进GC细胞转移。
关键词:  胃癌  肥胖相关蛋白  消皮素D  细胞迁移
DOI:10.3969/j.issn.1674-3806.2024.04.09
分类号:R 735.2
基金项目:国家自然科学基金项目(编号:82260579,81460380);广西医学高层次骨干人才培养“139”计划培养人选项目(编号:G202003016);广西中医药适宜技术开发与推广项目(编号:GZSY21-56);广西研究生教育创新计划项目(编号:YCSW2023240)
A study on the expressions of FTO and GSDMD in gastric cancer tissues and their mechanisms of action
HUANG Shanpei, WEI Erdan, ZHU Liye, NING Qiting, CHEN Xingmei, CHEN Ni, WU Jiangni, QIU Xinze, HUANG Jie′an, LIU Shiquan
Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
Abstract:
[Abstract] Objective To explore the expressions of fat mass and obesity-associated protein(FTO) and gasdermin D(GSDMD) in gastric cancer(GC) tissues and their mechanisms of action. Methods The differential expressions of FTO and GSDMD in GC tissues were analyzed by using the Tumor Immune Estimation Resource(TIMER) 2.0 database. Forty-five GC tissues and the corresponding paracancer tissues(3-5 cm away from the tumor margin) which were surgically excised from the patients in the Second Affiliated Hospital of Guangxi Medical University from January 2022 to March 2023 were collected, and the patients′ clinicopathological data were collected. Immunohistochemical staining method was used to detect the expressions of FTO and GSDMD in the tissues, and their correlations with the patients′ clinicopathological features were analyzed. AGS cells with low expression of FTO were constructed by transfecting low expression of FTO lentivirus(FTO low expression group), and the cells transfected with empty vector lentivirus were set up as the control group. Real-time fluorescence quantitative polymerase chain reaction(RT-PCR) was used to detect the levels of FTO mRNA and GSDMD mRNA expressions in the cells in the two groups. Cell scratch wound healing assay and cell migration test were used to analyze the cell migration ability in the two groups. Results The analysis results based on TIMER 2.0 database and the immunohistochemical staining results showed that FTO and GSDMD were highly expressed in GC tissues(P<0.05). The high expressions of FTO and GSDMD were closely related to the depth of tumor invasion and lymph node metastasis(P<0.05). The results of cell experiment showed that the level of GSDMD mRNA expression in the FTO low expression group was significantly lower than that in the control group(P<0.05), and the scratch healing rate was lower and the number of cell migration was less in the FTO low expression group, and the differences were statistically significant(P<0.05). Conclusion FTO may promote the metastasis of GC cells by regulating the expression of GSDMD.
Key words:  Gastric cancer(GC)  Fat mass and obesity-associated protein(FTO)  Gasdermin D(GSDMD)  Cell migration