Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers.
Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers.
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DOI：
10.1155/2010/821717
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发表时间：
2010
影响因子：
--
通讯作者：
Richer JK
中科院分区：
文献类型：
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作者：
Cochrane DR;Howe EN;Spoelstra NS;Richer JK
我们关注miR-200 c在乳腺癌、卵巢癌和子宫内膜癌中的独特作用。miR-200家族的成员靶向ZEB 1，ZEB 1是一种抑制E-钙粘蛋白和其他参与极性的基因的转录因子。我们证明了miR-200 c和ZEB 1之间的双负反馈环在一些细胞系中是有功能的，但不是所有细胞系。miR-200 c对侵袭性癌细胞的恢复导致迁移和侵袭的减少。这些影响是独立的E-钙粘蛋白状态。此外，我们观察到卵巢癌细胞中miR-200 c的恢复导致与层粘连蛋白的粘附减少。我们以前曾报道过，重新引入miR-200 c到缺乏miR-200 c表达的侵袭性细胞中可以恢复对紫杉醇的敏感性。我们现在证明这种能力是直接靶向III类β-微管蛋白（TUBB 3）的结果。将缺乏miR-200 c靶位点的TUBB 3表达构建体引入用miR-200 c模拟物转染的细胞中，对紫杉醇的敏感性没有变化。最后，我们观察到用miR-200 c模拟物转染的细胞和ZEB 1被稳定敲除的细胞的增殖减少，证明miR-200 c增强对紫杉醇敏感性的能力不是由于增殖速率增加。
We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers. Members of the miR-200 family target ZEB1, a transcription factor which represses E-cadherin and other genes involved in polarity. We demonstrate that the double negative feedback loop between miR-200c and ZEB1 is functional in some, but not all cell lines. Restoration of miR-200c to aggressive cancer cells causes a decrease in migration and invasion. These effects are independent of E-cadherin status. Additionally, we observe that restoration of miR-200c to ovarian cancer cells causes a decrease in adhesion to laminin. We have previously reported that reintroduction of miR-200c to aggressive cells that lack miR-200c expression restores sensitivity to paclitaxel. We now prove that this ability is a result of direct targeting of class III beta-tubulin (TUBB3). Introduction of a TUBB3 expression construct lacking the miR-200c target site into cells transfected with miR-200c mimic results in no change in sensitivity to paclitaxel. Lastly, we observe a decrease in proliferation in cells transfected with miR-200c mimic, and cells where ZEB1 is knocked down stably, demonstrating that the ability of miR-200c to enhance sensitivity to paclitaxel is not due to an increased proliferation rate.