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肌营养不良蛋白-α在胃癌中的表达、功能及其调控机制

Expression, function and regulatory mechanisms of dystrobrevin-α in gastric cancer

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【作者】 孙艺萌孙艺菲卢慧雯朱子锐姚君桥黄宝俊

【Author】 SUN Yimeng;SUN Yifei;LU Huiwen;ZHU Zirui;YAO Junqiao;HUANG Baojun;Radiation Treatment Room, Shengjing Hospital Affiliated to China Medical University;Department of Gastrointestinal Surgical Oncology, the First Hospital of China Medical University;Medical Science Center, Xiamen University;Division of Gastric Surgery, Liaoning Cancer Hospital;

【通讯作者】 黄宝俊;

【机构】 中国医科大学附属盛京医院放射治疗室中国医科大学附属第一医院胃肠肿瘤外科厦门大学医学部辽宁省肿瘤医院胃外科

【摘要】 目的:探讨肌营养不良蛋白-ɑ(DTNA)在胃癌组织中的表达特征、生物学功能及相关的调控机制。方法:基于公共数据库采用生物信息学方法分析预测DTNA基因在胃癌中的表达情况及与胃癌预后相关性。采用qPCR技术及免疫组化技术检测胃癌组织及细胞中DTNA的表达情况;采用卡方检验分析DTNA与胃癌临床病理特征之间的相关性,Kaplan-Meier生存分析法评估DTNA的表达水平与患者预后的关系。采用CCK-8、Transwell实验检测DTNA基因对胃癌MGC-803细胞增殖、迁移及侵袭的影响;RNA干扰、q PCR及WB实验检测远上游元件结合蛋白1(FUBP1)对MGC-803细胞中DTNA表达的影响。结果:生物信息学分析发现,DTNA在胃癌组织中表达高于癌旁组织且其高表达与胃癌的不良预后相关。DTNA在胃癌组织(P<0.000 1)和细胞(P<0.05)中表达上调,与T分期(P<0.001)及TNM分期(P=0.001)有正向关联,且与不良预后有正向关联(Log-Rank P=0.0039)。敲减DTNA可以显著抑制MGC-803细胞的增殖、迁移和侵袭能力(均P<0.01);FUBP1下调可降低DTNA的表达(P<0.01)。结论:DTNA在胃癌组织及细胞中表达上调且与病情进展及不良预后相关;敲减DTNA能抑制胃癌MGC-803细胞的增殖、迁移和侵袭,其表达受FUBP1调控。

【Abstract】 Objective: To investigate the expression characteristics, biological functions, and regulatory mechanisms of dystrobrevin-ɑ(DTNA) in gastric cancer tissues. Methods: Bioinformatics analysis based on public databases was used to predict DTNA expression in gastric cancer and its correlation with prognosis. Bioinformatics analysis based on public databases was used to predict DTNA expression in gastric cancer and its correlation with prognosis. qPCR and immunohistochemistry(IHC) were employed to detect DTNA expression in gastric cancer tissues and cells. The chi-square test analyzed the correlations between DTNA and clinicopathological features of gastric cancer, while KaplanMeier survival analysis assessed the relationship between DTNA expression and prognosis. CCK-8 and Transwell assays detected the effects of DTNA on the proliferation, migration, and invasion of gastric cancer MGC-803 cells. RNA interference, qPCR, and WB assay were used to examine the effects of far upstream element-binding protein 1(FUBP1) on DTNA expression in MGC-803 cells. Results: Bioinformatics analysis revealed upregulated DTNA expression in gastric cancer tissues versus adjacent tissues, correlating with poor prognosis. DTNA was upregulated in gastric cancer tissues(P < 0.0001) and cells(P < 0.05), showing positive correlations with T stage(P < 0.001), TNM stage(P = 0.001), and poor prognosis(Log-Rank P = 0.0039). DTNA knockdown significantly inhibited the proliferation, migration, and invasion abilities of MGC-803 cells(all P < 0.01). FUBP1 downregulation reduced DTNA expression(P < 0.01). Conclusion: DTNA is upregulated in gastric cancer tissues and cells and is correlated with disease progression and poor prognosis. DTNA knockdown inhibits the proliferation, migration, and invasion of gastric cancer cells, and its expression is regulated by FUBP1.

【基金】 沈阳市科技计划项目(No.21-173-9-78)
  • 【文献出处】 中国肿瘤生物治疗杂志 ,Chinese Journal of Cancer Biotherapy , 编辑部邮箱 ,2025年08期
  • 【分类号】R735.2
  • 【下载频次】14
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