TWEAK调控巨噬细胞外泌体中miRNA-7的表达抑制卵巢癌细胞侵袭和迁移的研究

发布时间：2018-04-13 01:24

本文选题：上皮性卵巢癌 + 巨噬细胞　；参考：《上海交通大学学报(医学版)》2017年06期

【摘要】：目的·检测TWEAK刺激后,巨噬细胞及其分泌的外泌体中miRNA-7的表达;探索TWEAK刺激后,巨噬细胞源性外泌体抑制上皮性卵巢癌细胞(HO8910-PM)侵袭和迁移的机制。方法·收集TWEAK刺激前后的巨噬细胞源性外泌体,并将其与HO8910-PM细胞共培养,real-time PCR检测巨噬细胞、巨噬细胞源性外泌体和共培养后HO8910-PM细胞中miRNA-7的表达;Western blotting检测共培养后HO8910-PM细胞中EGFR/AKT/ERK1/2信号通路的表达;Antagomi R-7处理降低巨噬细胞中miRNA-7表达后,收集TWEAK刺激前后的外泌体并进行transwell侵袭和迁移实验,观察HO8910-PM细胞侵袭和迁移能力的变化。结果·TWEAK刺激后,巨噬细胞内及其外泌体中miRNA-7的表达升高,并可上调HO8910-PM细胞中miRNA-7的表达,下调EGFR信号通路的表达。预先下调巨噬细胞中miRNA-7的表达后,巨噬细胞源性外泌体和共培养后HO8910-PM细胞中miRNA-7的表达降低,TWEAK刺激的巨噬细胞源性外泌体原先抑制HO8910-PM细胞转移的作用得到恢复。结论·miRNA-7在TWEAK刺激巨噬细胞分泌的外泌体中发挥重要作用,可通过抑制上皮性卵巢癌细胞中EGFR信号通路抑制其侵袭和迁移。
[Abstract]:Objective to detect the expression of miRNA-7 in macrophages and exocrine secreted by TWEAK, and to explore the mechanism of macrophage derived exocrine inhibition of invasion and migration of epithelial ovarian cancer cell line HO8910-PMM stimulated by TWEAK.Methods macrophage derived exocrine bodies were collected before and after TWEAK stimulation and were co-cultured with HO8910-PM cells to detect macrophages by real-time PCR.Expression of miRNA-7 in macrophage derived exocrine and co-cultured HO8910-PM cells. Western blotting was used to detect the expression of EGFR/AKT/ERK1/2 signaling pathway in co-cultured HO8910-PM cells. Antagomi R-7 treatment decreased miRNA-7 expression in macrophages.The exocrine bodies were collected before and after TWEAK stimulation, and the invasion and migration of HO8910-PM cells were observed by transwell invasion and migration experiments.Results after TWEAK stimulation, the expression of miRNA-7 in macrophages and its exocrine increased, and the expression of miRNA-7 in HO8910-PM cells was up-regulated, and the expression of EGFR signal pathway was down-regulated.After down-regulating the expression of miRNA-7 in macrophages, the expression of miRNA-7 in macrophages derived from exocrine and co-cultured HO8910-PM cells decreased, and the inhibitory effect of TWEAK-stimulated macrophage derived exocrine on the metastasis of HO8910-PM cells was recovered.Conclusion miRNA-7 plays an important role in the secretion of macrophages stimulated by TWEAK and can inhibit the invasion and migration of epithelial ovarian cancer cells by inhibiting the EGFR signaling pathway.
【作者单位】：上海交通大学医学院附属仁济医院妇产科上海市妇科肿瘤重点实验室;
【基金】：国家自然科学基金(81272884) 上海市卫生和计划生育委员会科研项目(ZHYY-ZXYJHZX-2-06) 上海市教育委员会高峰高原学科建设计划(20161412)~~
【分类号】：R737.31

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