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KCNQ1OT1/miR-217/ZEB1 feedback loop facilitates cell migration and epithelial-mesenchymal transition in colorectal cancer

机译:KCNQ1OT1 / miR-217 / Zeb1反馈回路有助于细胞迁移和结直肠癌中皮 - 间充质过渡

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摘要

Long noncoding RNAs are widely acknowledged as a group of regulatory factors in various diseases, especially in cancers. KCNQ1 overlapping transcript 1 (KCNQ1OT1) has been reported as oncogene in human cancers. However, the role of KCNQ1OT1 in colorectal cancer (CRC) has not been fully explained. Based on the database analysis, KCNQ1OT1 was highly expressed in CRC samples and predicted the poor prognosis for CRC patients. Functional experiments revealed that KCNQ1OT1 knockdown negatively affected the proliferation, migration and epithelial-mesenchymal transition (EMT) in CRC cells. Moreover, we identified the cytoplasmic localization of KCNQ1OT1 in CRC cells, indicating the post-transcriptional regulation of KCNQ1OT1 on gene expression. Mechanism experiments including RNA Immunoprecipitation (RIP) assay and dual luciferase reporter assays verified that KCNQ1OT1 acted as a competing endogenous RNA (ceRNA) in CRC by sponging microRNA-217 (miR-217) to up-regulate the expression of zinc finger E-box binding homeobox 1 (ZEB1). Further mechanism investigation revealed that ZEB1 enhanced the transcription activity of KCNQ1OT1 by acting as a transcription activator. Finally, rescue assays were designed to demonstrate the effect of KCNQ1OT1-miR-217-ZEB1 feedback loop on proliferation, migration, and EMT of CRC cells. In brief, our research findings revealed that ZEB1-induced upregulation of KCNQ1OT1 improved the proliferation, migration and EMT formation of CRC cells via regulation of miR-217/ZEB1 axis.
机译:长期非编码RNA被广泛被认为是各种疾病的一组调控因子,特别是在癌症中。 KCNQ1重叠的转录物1(KCNQ1OT1)已被报告为人类癌症中的癌基因。然而,KCNQ1OT1在结肠直肠癌(CRC)中的作用尚未得到充分解释。基于数据库分析,KCNQ1OT1在CRC样品中高度表达,并预测了CRC患者的预后差。功能实验表明,KCNQ1OT1敲低对CRC细胞中的增殖,迁移和上皮 - 间充质转换(EMT)造成负面影响。此外,我们鉴定了CRC细胞中KCNQ1OT1的细胞质定位,表明KCNQ101对基因表达的转录后调节。包括RNA免疫沉淀(RIP)测定和双荧光素酶报告组测定的机制实验证实,KCNQ1OT1通过海绵MicroRNA-217(miR-217)来上调锌手指E-Box的表达,作为CRC中的竞争内源性RNA(Cerna)。装订Homeobox 1(Zeb1)。进一步的机制调查显示,Zeb1通过作为转录活化剂而增强了KCNQ1OT1的转录活性。最后,设计抢救测定以证明KCNQ1OT1-MIR-217-ZEB1反馈回路对CRC细胞的增殖,迁移和EMT的影响。简而言之,我们的研究结果表明,Zeb1诱导的KCNQ1OT1的上调通过MiR-217 / Zeb1轴的调节改善了CRC细胞的增殖,迁移和EMT形成。

著录项

  • 来源
    《Cancer biology & therapy》 |2019年第6期|共11页
  • 作者单位

    Nanjing Med Univ Nanjing Drum Tower Hosp Clin Coll Comprehens Canc Ctr 321 Zhongshan Rd;

    Xuzhou Med Univ Affiliated Huaian Hosp Dept Tradit Chinese Med Huaian Jiangsu Peoples R China;

    Nanjing Univ Nanjing Drum Tower Hosp Comprehens Canc Ctr Clin Canc Inst Med Sch Nanjing;

    Nanjing Univ Nanjing Drum Tower Hosp Comprehens Canc Ctr Clin Canc Inst Med Sch Nanjing;

    Nanjing Univ Nanjing Drum Tower Hosp Comprehens Canc Ctr Clin Canc Inst Med Sch Nanjing;

    Nantong Univ Affiliated Hosp Radiotherapy Oncol Nantong Jiangsu Peoples R China;

    Nantong Univ Affiliated Hosp Radiotherapy Oncol Nantong Jiangsu Peoples R China;

    Nanjing Univ Nanjing Drum Tower Hosp Comprehens Canc Ctr Clin Canc Inst Med Sch Nanjing;

    Nanjing Med Univ Nanjing Drum Tower Hosp Clin Coll Comprehens Canc Ctr 321 Zhongshan Rd;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    KCNQ1OT1; miR-217; ZEB1; colorectal cancer; migration;

    机译:kcnq1ot1;mir-217;zeb1;结肠直肠癌;迁移;

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