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Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer  期刊论文   WOS高被引论文 WOS热点论文

  • 编号:
    3BCBDA8DA609469E37E43B75C949D804
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  • 语种:
    英文
  • 期刊:
    JOURNAL OF HEMATOLOGY & ONCOLOGY ISSN:1756-8722 2020 年 13 卷 1 期 ; NOV 19
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  • 摘要:

    Background Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown. Methods Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages. Results In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NF kappa B/p65/miR-934 positive feedback loop in CRC cells. Conclusions These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.

  • 推荐引用方式
    GB/T 7714:
    Zhao Senlin,Mi Yushuai,Guan Bingjie, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer [J].JOURNAL OF HEMATOLOGY & ONCOLOGY,2020,13(1).
  • APA:
    Zhao Senlin,Mi Yushuai,Guan Bingjie,Zheng Binbin,&Li Dawei.(2020).Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer .JOURNAL OF HEMATOLOGY & ONCOLOGY,13(1).
  • MLA:
    Zhao Senlin, et al. "Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer" .JOURNAL OF HEMATOLOGY & ONCOLOGY 13,1(2020).
  • 入库时间:
    11/2/2020 12:00:00 AM
  • 更新时间:
    11/2/2020 12:00:00 AM
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