Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells
Overexpression of miR-429 induces mesenchymal-to-epithelial transition (MET) in metastatic ovarian cancer cells
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DOI：
10.1016/j.ygyno.2010.12.339
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发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
McDonald, John F.
中科院分区：
文献类型：
--
作者：
Chen, Jing;Wang, Lijuan;McDonald, John F.
目标。卵巢癌(OC)是所有妇科恶性肿瘤中最致命的一种，主要原因是高转移细胞从原发肿瘤中脱落并随后扩散到整个腹膜腔。由于位于原发肿瘤周围的OC细胞的上皮向间充质转化(EMT)在这一过程中是必不可少的，因此可以阻断EMT的分子干预具有潜在的临床意义。MiR200家族的成员已经被认为与其他癌症的EMT有关。我们的目的是确定miR200家族microRNAs是否可能参与卵巢癌的EMT，以及在减少OC转移方面的潜在治疗价值。采用定量逆转录聚合酶链式反应(qRT-PCR)技术检测两株不同转移潜能的卵巢癌细胞系的基因表达谱。从分子水平(qRT-PCR和微阵列)和功能水平(形态、迁移、侵袭和锚定独立性检测)观察miR-200家族microRNA(miR-429)过表达对转移OC细胞的影响。两个具有不同转移潜能的OC细胞系的分子图谱表明，先前建立的上皮和间充质细胞生物标记物包括E-钙粘蛋白、ZEB1、ZEB2、miR-205和miR-200家族microRNAs存在显著差异。MiR-200家族成员miR-429在间充质样癌细胞中的异位过表达导致间充质表型逆转(MET)。我们的结果表明miR-429可能不仅是卵巢癌EMT的一个有用的生物标志物，而且在减少卵巢癌转移方面也有潜在的治疗价值。(C)2010 Elsevier Inc.保留所有权利。
Objective. Ovarian cancer (OC) is the most lethal of all gynecological malignancies primarily due to the sloughing-off of highly metastatic cells from primary tumors and their subsequent spread throughout the peritoneal cavity. Since the epithelial-to-mesenchymal transition (EMT) of OC cells located at the periphery of primary tumors is essential to this process, molecular interventions that can block EMT are of potential clinical significance. Members of the miR200 family of microRNAs have been implicated in EMT in other cancers. Our purpose was to determine if miR200 family microRNAs may be involved in EMT in OC and of potential therapeutic value in reducing OC metastasis.Methods. Gene expression profiles of two OC cell lines with different metastatic potentials were monitored using qRT-PCR (quantitative reverse transcription polymerase chain reaction). The effect of over-expression of a miR-200 family microRNA (miR-429) in metastatic OC cells was monitored on molecular (qRT-PCR and microarray) and functional (morphology, migration, invasiveness and anchorage independence assays) levels.Results. Molecular profiling of two OC cell lines with differing metastatic potentials identified significant differences in previously established epithelial and mesenchymal cell biomarkers including E-cadherin, ZEB1, ZEB2, miR-205 and miR-200 family microRNAs. Ectopic overexpression of miR-429, a member of the miR-200 family of microRNAs, in mesenchymal-like OC cells resulted in reversal of the mesenchymal phenotype (mesenchymal epithelial transition, MET).Conclusions. Our results indicate that miR-429 may not only be a useful biomarker of EMT in ovarian cancer, but also of potential therapeutic value in abating OC metastasis. (C) 2010 Elsevier Inc. All rights reserved.