MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition.
MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition.
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DOI：
10.1186/1757-2215-6-50
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发表时间：
2013-07-10
影响因子：
4
通讯作者：
Dou J
中科院分区：
文献类型：
--
作者：
Chen D;Zhang Y;Wang J;Chen J;Yang C;Cai K;Wang X;Shi F;Dou J
肿瘤干细胞被认为是肿瘤复发和转移的种子细胞。微小RNA（microRNAs，miRNAs）通过调控上皮-间质转化（epithelial-mesenchymal transition，EMT）在肿瘤的转移过程中发挥重要作用。本研究旨在探讨miRNA-200 c过表达对上皮性卵巢癌（EOC）CSCs EMT、致瘤性和转移的影响。通过使用磁激活细胞分选系统从人卵巢癌细胞系SKOV 3中分离EOC CD 117 + CD 44 +CSCs，然后选择慢病毒miR-200 c转导的CSCs用于研究。进行集落形成、伤口愈合、体外细胞迁移和体内肿瘤进展的测定。与非CD 117 + CD 44 + CSC相比，CD 117 + CD 44 + CSC中的miR-200 c表达降低。然而，miR-200 c在CD 117 + CD 44 +CSCs中的稳定过表达导致ZEB-1和Vimentin表达显著下调，E-cadherin表达上调，体外集落形成、迁移和侵袭能力降低。重要的是，miR-200 c过表达通过抑制EMT显著抑制了裸鼠体内CD 117 + CD 44 + CSC异种移植物生长和肺转移。此外，ZEB-1的下调在CD 117 + CD 44 + CSC中显示出与miR-200 c过表达相同的功效。本研究的这些发现表明，miR-200 c过表达可能被认为是临床试验中EOC CD 117 + CD 44 + CSC的关键方法。
Cancer stem cells (CSCs) are believed to be ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) can play an important role in the progression of primary tumor towards metastasis by regulating the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c overexpression on the EMT, tumorigenicity and metastasis of epithelial ovarian cancer (EOC) CSCs. The EOC CD117+CD44+CSCs were isolated from the human ovarian cancer cell line SKOV3 by using a magnetic-activated cell sorting system, and the lentivirus miR-200c transduced CSCs were then selected for the study. The assays of colony forming, wound healing, cellular migration in vitro and tumor progression in vivo were performed. The miR-200c expression was reduced in the CD117+CD44+CSCs compared with the non-CD117+CD44+CSCs. However, the stable overexpression of the miR-200c in the CD117+CD44+CSCs resulted in a significant down-regulation of ZEB-1 and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, migratory and invasion in vitro. Importantly, the miR-200c overexpression significantly inhibited the CD117+CD44+CSCs xenograft growth and lung metastasis in vivo in nude mice by inhibition of the EMT. In addition, the down-regulation of ZEB-1 showed the same efficacy as the miR-200c overexpression in the CD117+CD44+CSCs. These findings from this study suggest that the miR-200c overexpression may be considered a critical approach for the EOC CD117+CD44+CSCs in clinical trials.
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DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
4.7
作者：
Chen, Jing;Wang, Lijuan;McDonald, John F.
通讯作者：
McDonald, John F.
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
1.6
作者：
Dou, J.;Li, Y.;Gu, N.
通讯作者：
Gu, N.