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MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells   [复制链接]

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楼主
发表于 2010-1-7 15:24 |只看该作者 |正序浏览 |打印
PLoS One. 2009 Aug 28;4(8):e6816.
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$ {& h- G  j4 A' r5 eMicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells.( Y5 L! m3 A3 Q$ T/ W0 \- I
Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, Xiang D, Desano JT, Bommer GT, Fan D, Fearon ER, Lawrence TS, Xu L.
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Department of Radiation Oncolog, University of Michigan, Ann Arbor, Michigan, United States of America.$ ]0 q9 x$ k6 M: y8 L9 f: v
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BACKGROUND: MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting pancreatic cancer stem cells.
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( k5 p; A2 r- g% d% {# J* ZPMID: 19714243 [PubMed - in process]
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发表于 2011-1-20 22:06 |只看该作者
没看太懂,需要学习

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发表于 2010-7-23 09:16 |只看该作者
先看看

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发表于 2010-3-24 17:06 |只看该作者
干细胞之家微信公众号
学习谢谢

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发表于 2010-2-28 18:09 |只看该作者
不过CD44/CD133能代表PAC中CSC的表型吗?

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地板
发表于 2010-2-28 18:06 |只看该作者
辛苦啦!6 O& i- y# g* ^' D! y# W( S: u
不错,拜读一下!

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报纸
发表于 2010-2-22 08:45 |只看该作者
kankan

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板凳
发表于 2010-1-31 14:36 |只看该作者
谢谢,已下载学习了。

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藤椅
发表于 2010-1-20 08:13 |只看该作者
真感谢

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沙发
发表于 2010-1-8 17:31 |只看该作者
楼主辛苦
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