首页> 中文期刊> 《中国癌症杂志》 >miR-26a靶向MMP16参与调控胃癌细胞侵袭作用研究

miR-26a靶向MMP16参与调控胃癌细胞侵袭作用研究

         

摘要

Background and purpose:Invasion and metastasis lead to poor prognosis in gastric cancer. In this study, we investigated the potential function of miR-26a in gastric cancer.Methods:Real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of miR-26a in gastric cancer cells.In vitro CCK-8 assay, cloning formation assay and Matrigel-Transwell assay were used to evaluate the proliferation, migration and invasion of gastric cancer cells. A luciferase reporter assay was also conducted to confirm that matrix metallo-proteinase-16 (MMP16) is a direct target of miR-26a.Results:miR-26a was down-regulated in gastric cancer tissues compared with that in non-cancerous tissues. Functional studies showed that miR-26a inhibited cell proliferation, col-ony formation, cell motility and invasion. However, miR-26a had no effect on cell proliferation. We also characterized MMP16 as a direct target of miR-26a. We showed that knocking down MMP16 in gastric cancer cells signiifcantly de-creased MMP16 expression and inhibited cell invasion, whereas ectopic MMP16 expression signiifcantly abrogated the suppressed cell invasion induced by miR-26a.Conclusion:miR-26a suppresses gastric cancer cell invasion by targeting MMP16. miR-26a could represent a potential therapeutic target for gastric cancer.%背景与目的:胃癌发生侵袭转移是导致患者预后不良的重要因素。本研究旨在明确miR-26a在调控胃癌细胞运动侵袭中的作用及其可能机制。方法:通过实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测胃癌组织细胞中miR-26a表达情况,体外通过CCK-8法、平板克隆形成实验和Matrigel-Transwell实验评价miR-26a对人胃癌细胞增殖、运动和侵袭能力的影响。荧光素酶报告基因系统评估miR-26a对下游靶基因的调控作用。结果:胃癌组织中miR-26a表达较癌旁组织明显下降。miR-26a体外对胃癌细胞增殖无明显影响,但可显著抑制胃癌细胞的运动和侵袭。相反,抑制miR-26a表达可促进胃癌细胞的侵袭能力。生物信息学分析提示,基质金属蛋白酶16(matrix metalloproteinase 16,MMP16)为miR-26直接调控靶基因,miR-26a可抑制胃癌细胞MMP16 miRNA和蛋白的表达。荧光素酶报告基因检测提示,miR-26a可与MMP16 mRNA 3’UTR结合诱导其转录后抑制。进一步研究提示,MMP16 siRNA对胃癌细胞侵袭具有模拟miR-26a作用,而过表达MMP16可拮抗miR-26a对胃癌细胞侵袭的影响。结论:miR-26a可通过靶向MMP16来抑制胃癌细胞运动侵袭,miR-26a可作为抑制胃癌细胞侵袭的重要干预靶点。

著录项

  • 来源
    《中国癌症杂志》 |2016年第10期|813-819|共7页
  • 作者单位

    复旦大学附属肿瘤医院肿瘤内科;

    复旦大学上海医学院肿瘤学系;

    上海 200032;

    复旦大学附属肿瘤医院肿瘤内科;

    复旦大学上海医学院肿瘤学系;

    上海 200032;

    中国人民解放军第四五五医院消化内科;

    上海 200052;

    复旦大学附属肿瘤医院肿瘤内科;

    复旦大学上海医学院肿瘤学系;

    上海 200032;

    复旦大学附属肿瘤医院肿瘤内科;

    复旦大学上海医学院肿瘤学系;

    上海 200032;

    复旦大学附属肿瘤医院肿瘤内科;

    复旦大学上海医学院肿瘤学系;

    上海 200032;

  • 原文格式 PDF
  • 正文语种 chi
  • 中图分类 胃肿瘤;
  • 关键词

    miR-26a; 胃癌; 基质金属蛋白酶16; 侵袭;

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