MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1.
MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1.
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DOI：
10.1186/1476-4598-10-99
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发表时间：
2011-08-18
期刊：
影响因子：
37.3
通讯作者：
Sakuragi N
中科院分区：
文献类型：
--
作者：
Dong P;Kaneuchi M;Watari H;Hamada J;Sudo S;Ju J;Sakuragi N
上皮-间质转化（Epithelial-mesenchymal transition， EMT）是肿瘤转移的关键过程。癌基因/自我更新因子BMI-1已被证明在癌细胞中诱导EMT。最近的研究表明，非编码microrna （mirna）在EMT中起着重要的调节作用。本研究的目的是确定BMI-1在诱导子宫内膜癌（EC）细胞EMT中的作用，以及miRNA在控制BMI-1表达中的可能作用。我们在一组EC细胞系中评估了BMI-1基因的表达，发现其与侵袭能力有很强的相关性。在侵袭性间充质型EC细胞中，稳定沉默BMI-1可上调上皮标记物E-cadherin，下调间充质标记物Vimentin，并在体外显著降低细胞侵袭。此外，我们发现miR-194通过直接结合BMI-1 3'-非翻译区3'-UTR来抑制BMI-1的表达。在体外，miR-194在EC细胞中的异位表达通过恢复E-cadherin、降低Vimentin表达和抑制细胞侵袭，诱导间充质向上皮转化（MET）。此外，BMI-1敲低抑制体外EC细胞增殖和克隆生长，与p16表达增加或干细胞和化疗耐药标志物（SOX-2， KLF4和MRP-1）表达减少相关。这些发现证明了BMI-1促进EC细胞侵袭的新机制，并且miR-194抑制BMI-1可能具有抑制EC转移的治疗潜力。
Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression. We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion in vitro. Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion in vitro. Moreover, BMI-1 knockdown inhibited in vitro EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1). These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.
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MiR-218通过靶向Robo1受体抑制胃癌的侵袭和转移。
影响因子：
4.5
作者：
Tie J;Pan Y;Zhao L;Wu K;Liu J;Sun S;Guo X;Wang B;Gang Y;Zhang Y;Li Q;Qiao T;Zhao Q;Nie Y;Fan D
通讯作者：
Fan D
影响因子：
8
作者：
Hoenerhoff, M. J.;Chu, I.;Barkan, D.;Liu, Z-y;Datta, S.;Dimri, G. P.;Green, J. E.
通讯作者：
Green, J. E.
影响因子：
5
作者：
Sasaki, Motoko;Ikeda, Hiroko;Nakanuma, Yasuni
通讯作者：
Nakanuma, Yasuni
影响因子：
37.3
作者：
Dong, Peixin;Xu, Zhujie;Feng, Youji
通讯作者：
Feng, Youji
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB