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miR-381 overcomes cisplatin resistance in breast cancer by targeting MDR1

机译:MiR-381通过靶向MDR1克服了乳腺癌中的顺铂抗性

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摘要

Increasing evidence suggests the involvement of microRNA-381 (miR-381) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in breast cancer chemoresistance are still not well elucidated. In the present study, we aimed to investigate the functional role of miR-381 in cisplatin (DDP) resistance of breast cancer and discover the underlying molecular mechanism. The expression levels of miR-381 and MDR1 were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis in breast cancer tissues and cell lines. The DDP sensitivity and cell apoptosis of breast cancer cells were determined by MTT assay and flow cytometric analysis, respectively. The relationship between miR-381 and MDR1 was explored by target prediction and luciferase reporter analysis. miR-381 was decreased in DDP-resistant breast cancer tissues and cell lines. Low miR-381 expression was correlated with poor prognosis of breast cancer patients. miR-381 overexpression improved DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Conversely, miR-381 inhibition lowered the response of MCF-7 and MDA-MB-231 to DPP. Moreover, miR-381 could directly suppress multidrug resistance 1 (MDR1) expression. MDR1 knockdown could overcome DDP resistance in MCF-7/DDP and MDA-MB-231/DDP cells, while MDR1 overexpression led to DDP resistance in MCF-7 and MDA-MB-231 cells. Notably, MDR1 overexpression counteracted the inductive effect of miR-381 mimics on DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. On the contrary, miR-381 inhibition-mediated DDP resistance in MCF-7 and MDA-MB-231 cells was reversed by MDR1 knockdown. In summary, miR-381 could overcome DDP resistance of breast cancer by directly targeting MDR1, providing a novel therapeutic target for breast cancer chemoresistance.
机译:越来越多的证据表明MicroRNA-381(miR-381)参与癌症治疗的化学抑制性。然而,其乳腺癌化学抑制的功能和分子机制仍然阐明。在本研究中,我们旨在探讨miR-381在乳腺癌的顺铂(DDP)抗性的功能作用,并发现潜在的分子机制。通过定量实时PCR(QRT-PCR)和乳腺癌组织和细胞系中的Western印迹分析检测miR-381和MDR1的表达水平。通过MTT测定和流式细胞术分析测定乳腺癌细胞的DDP敏感性和细胞凋亡。靶预测和荧光素酶报告分析探索了MIR-381和MDR1之间的关系。在DDP抗性乳腺癌组织和细胞系中降低miR-381。低miR-381表达与乳腺癌患者的预后不良相关。 miR-381过表达改善了MCF-7 / DDP和MDA-MB-231 / DDP细胞的DDP敏感性。相反,miR-381抑制降低了MCF-7和MDA-MB-231至DPP的响应。此外,MIR-381可以直接抑制多药电阻1(MDR1)表达。 MDR1敲低可以克服MCF-7 / DDP和MDA-MB-231 / DDP细胞中的DDP电阻,而MDR1过表达导致MCF-7和MDA-MB-231细胞中的DDP电阻。值得注意的是,MDR1过度表达抵消MIR-381模拟MCF-7 / DDP和MDA-MB-231 / DDP细胞DDP敏感性的诱导效果。相反,MIR-381抑制MCF-7和MDA-MB-231细胞中的抑制介导的DDP电阻通过MDR1敲低反转。总之,MIR-381可以通过直接靶向MDR1来克服乳腺癌的DDP抗性,为乳腺癌化学抑制性提供新的治疗靶标。

著录项

  • 来源
    《Cell biology international.》 |2019年第1期|共10页
  • 作者单位

    Nanjing Drum Tower Hosp Dept Gen Surg Nanjing 210008 Jiangsu Peoples R China;

    Nanjing Med Univ Drum Tower Clin Med Coll Dept Gen Surg Nanjing 210008 Jiangsu Peoples R China;

    Nanjing Med Univ Drum Tower Clin Med Coll Dept Gen Surg Nanjing 210008 Jiangsu Peoples R China;

    Nanjing Med Univ Drum Tower Clin Med Coll Dept Gen Surg Nanjing 210008 Jiangsu Peoples R China;

    Nanjing Drum Tower Hosp Dept Gen Surg Nanjing 210008 Jiangsu Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    breast cancer; cisplatin; miR-381; multidrug resistance 1 (MDR1);

    机译:乳腺癌;顺铂;miR-381;多药电阻1(MDR1);

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