Exosome-mediated miR-222 transferring: An insight into NF-κ-mediated breast cancer metastasis
Exosome-mediated miR-222 transferring: An insight into NF-κ-mediated breast cancer metastasis
复制标题
外泌体介导的 miR-222 转移：深入了解 NF-kappaB 介导的乳腺癌转移
DOI：
10.1016/j.yexcr.2018.05.014
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发表时间：
2018-08-01
影响因子：
3.7
通讯作者：
Tang, Jinhai
中科院分区：
文献类型：
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作者：
Ding, Jiaji;Xu, Zhi;Tang, Jinhai
导致治疗失败和预后不良的远处器官转移亚型是晚期乳腺癌（BCa）患者治疗的主要障碍。新的证据表明，外泌体充当局部肿瘤微环境中各种类型细胞之间细胞间通讯的介质。本研究旨在调查 BCa 衍生的外泌体是否能够在细胞间转移 miR-222 以促进 BCa 转移进展。结果显示，外泌体miR-222在有淋巴转移的BCa患者中高表达。一致地，外泌体 miR-222 水平升高与 BCa 细胞系的高攻击性密切相关。 miR-222 促进 BCa 细胞的攻击性在体外和体内均得到证实。从机制上讲，miR-222 直接靶向肿瘤抑制基因 PDLIM2，从而激活 NF-kappa B 信号通路。总之，外泌体 miR-222 的水平与 BCa 转移进展相关。外泌体转移的 miR-222 促进 BCa 细胞的迁移和侵袭。 miR-222 通过下调 PDLIM2 从而激活 NF-kappa B 来促进 BCa 细胞的致瘤性。
The subtypes of distant-organ metastasis led to treatment failure and poor prognosis are major obstacles in the management of patients with advanced breast cancer (BCa). Emerging evidences demonstrated that exosomes act as mediators for intercellular communication between various types of cells in the local tumor micro environment. The present study aims to investigate whether BCa-derived exosomes are capable of cell-cell transferring miR-222 for BCa metastatic progression. Results showed that exosomal miR-222 is highly expressed in BCa patients with lymphatic metastasis. Consistently, the elevated levels of exosomal miR-222 are closely correlated with the high aggressivity of BCa cell lines. miR-222 promoting the aggressivity of BCa cells was confirmed in vitro and in vivo. Mechanistically, miR-222 directly targets PDLIM2, a tumor suppressor gene, leading to activation of NF-kappa B signal pathway. In conclusion, the levels of exosomal miR-222 are correlated with BCa metastatic progression. Exosome-transferred miR-222 promotes migration and invasion of BCa cells. miR-222 contributes to tumorigenicity of BCa cells through down-regulation of PDLIM2 and consequently activating NF-kappa B.