›› 2017, Vol. 37 ›› Issue (6): 726-.doi: 10.3969/j.issn.1674-8115.2017.06.003

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Exosomal miRNA-7 from TWEAK-stimulated macrophages inhibiting the invasion and migration of ovarian cancer cells

LI Dong, HU Yuan, WU An-yue, QIU Xing-di, QIU Li-hua   

  1. Department of Gynecology and Obstetrics, Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2017-06-28 Published:2017-07-05
  • Supported by:

    National Natural Science Foundation of China, 81272884; Foundation of Shanghai Municipal Commission of Health and Family Planning, ZHYYZXYJHZX-2-06; Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support, 20161412

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Abstract:

 Objective · To determine the expression of miRNA-7 in TWEAK-stimulated macrophages and their secreted exosomes; to investigate the role of exosomal miRNA-7 from TWEAK-stimulated macrophages in modulating the metastasis of epithelial ovarian cancer (EOC) cells.  Methods · Real-time PCR analysis was used to determine the miRNA-7 expression in TWEAK-stimulated macrophages, their exosomes and recipient HO8910-PM cells. The activity of EGFR signaling pathway in HO8910-PM cells was detected by Western blotting analysis. AntagomiR-7 was used to downregulate the miRNA-7 expressions in macrophage exosomes and then their effect on metastasis of HO8910-PM cells was examined by transwell assay.  Results · TWEAK increased the levels of miRNA-7 in macrophages and their secreted exosomes and also resulted in an elevated level of miRNA-7 in recipient HO8910PM cells, which eventually reduced the activity of EGFR/AKT/ERK1/2 pathway. Pre-transfection of antagomiR-7 remarkably decreased the levels of miRNA-7 in macrophages, their secreted exosomes and the recipient EOC cells, with the enhancement of HO8910-PM metastasis.  Conclusion · Exosomal miRNA-7 from TWEAK-stimulated macrophages plays a critical role in suppressing the metastasis of EOC cells by attenuation of EGFR signaling
 pathway.

Key words: epithelial ovarian cancer, macrophages, exosome, TWEAK, cell invasion and migration