MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3.
MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3.
复制标题
血小板源性微泡递送的 MicroRNA-223 通过靶向肿瘤抑制因子 EPB41L3 促进肺癌细胞侵袭
DOI：
10.1186/s12943-015-0327-z
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发表时间：
2015-03-11
期刊：
影响因子：
37.3
通讯作者：
Zen K
中科院分区：
文献类型：
--
作者：
Liang H;Yan X;Pan Y;Wang Y;Wang N;Li L;Liu Y;Chen X;Zhang CY;Gu H;Zen K
与无血行转移的肺癌患者相比，血行转移的肺癌患者显示出显著增加的血小板计数和聚集。肺癌血行转移与血小板活化之间的相关机制尚不清楚。在本研究中，我们探讨了来自血小板的microRNA-223（miR-223）在调节肺癌细胞侵袭中的作用。我们的研究结果表明，NSCLC患者血小板中miR-223的水平高于健康受试者。与健康受试者相比，NSCLC患者血小板分泌微泡（P-MV）中miR-223的浓度也增加。用P-MV孵育人肺癌A549细胞导致miR-223快速递送到A549细胞中，其中血小板miR-223靶向EPB 41 L3，从而促进A549细胞侵袭。P-MV减少A549细胞中EPB 41 L3但促进肿瘤细胞侵袭的作用可以通过用miR-223转染miR-223来耗尽miR-223而在很大程度上消除。通过用EPB 41 L3 siRNA或miR-223模拟物转染细胞直接下调EPB 41 L3，进一步验证了EPB 41 L3在抑制A549细胞侵袭中的作用。我们的研究首次证明，血小板通过P-MV分泌的miR-223可以通过靶向肿瘤抑制因子EPB 41 L3促进肺癌细胞侵袭。本文的在线版本（doi：10.1186/s12943-015-0327-z）包含补充材料，可供授权用户使用。
Patients with hematogenous metastatic lung cancer displayed significantly increased platelet count and aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlying the correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown. In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulating lung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level of miR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles (P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of human lung cancer A549 cells with P-MVs resulted in rapid delivery of miR-223 into A549 cells, in which platelet miR-223 targeted EPB41L3 and thus promoted A549 cell invasion. The effect of P-MVs on reducing EPB41L3 in A549 cells but promoting tumor cell invasion could be largely abolished by depletion of miR-223 via transfection with miR-223 antagomir. The role of EPB41L3 in inhibiting A549 cell invasion was further validated by directly downregulating EPB41L3 via transfecting cells with EPB41L3 siRNA or miR-223 mimic. Our study demonstrates for the first time that platelet-secreted miR-223 via P-MVs can promote lung cancer cell invasion via targeting tumor suppressor EPB41L3. The online version of this article (doi:10.1186/s12943-015-0327-z) contains supplementary material, which is available to authorized users.