MiR-93 enhances angiogenesis and metastasis by targeting LATS2
MiR-93 enhances angiogenesis and metastasis by targeting LATS2
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DOI：
10.4161/cc.22670
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发表时间：
2012-12-01
期刊：
影响因子：
4.3
通讯作者：
Yang, Burton B.
中科院分区：
文献类型：
--
作者：
Fang, Ling;Du, William W.;Yang, Burton B.
在此，我们报道了miR-93，一个与miR-17-92簇的一个同源簇miR-106 B中的一个类似于25簇的miRNA，在人乳腺癌组织中显著上调。我们在MT-1人乳腺癌细胞系中稳定表达miR-93，发现miR-93细胞形成的肿瘤比对照细胞形成的肿瘤含有更多的血管。共培养实验表明，MT-1细胞与内皮细胞的粘附活性较高，并能与内皮细胞形成更大、更多的管状结构。在小鼠转移模型中进行肺转移测定，并且发现miR-93的表达促进肿瘤细胞向肺组织的转移。在细胞培养中，miR-93的表达增强了细胞存活和侵袭。我们研究了介导miR-93作用的潜在靶点，发现大肿瘤抑制因子同源2（LATS 2）是miR-93的靶点。较高水平的LATS 2与肿瘤块中的细胞死亡相关。LATS 2表达沉默促进细胞存活、管形成和侵袭，而LATS 2的异位表达降低细胞存活和侵袭。这些发现表明miR-93通过抑制LATS 2表达促进肿瘤血管生成和转移。我们的研究结果表明，抑制miR-93的功能可能是一种可行的方法来抑制肿瘤转移。
Here we report that miR-93, a miRNA in the miR-106B similar to 25 cluster, a paralog of the miR-17-92 cluster, was significantly upregulated in human breast carcinoma tissues. We stably expressed miR-93 in the MT-1 human breast carcinoma cell line and found that tumors formed by the miR-93 cells contained more blood vessels than those formed by the control cells. Co-culture experiments indicated that the MT-1 cells displayed a high activity of adhesion with endothelial cells and could form larger and more tube-like structures with endothelial cells. Lung metastasis assays were performed in a mouse metastatic model, and it was found that expression of miR-93 promoted tumor cell metastasis to lung tissue. In cell culture, expression of miR-93 enhanced cell survival and invasion. We examined the potential target that mediated miR-93's effects and found that the large tumor suppressor, homology 2 (LATS2) was a target of miR-93. Higher levels of LATS2 were associated with cell death in the tumor mass. Silencing LATS2 expression promoted cell survival, tube formation and invasion, while ectopic expression of LATS2 decreased cell survival and invasion. These findings demonstrated that miR-93 promoted tumor angiogenesis and metastasis by suppressing LATS2 expression. Our results suggest that the inhibition of miR-93 function may be a feasible approach to repress tumor metastasis.