Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.

Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.
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DOI:
10.1016/j.cell.2009.07.011
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发表时间:
2009-08-07
期刊:
影响因子:
64.5
通讯作者:
Clarke MF
Clarke MF
中科院分区:
生物学1区
文献类型:
--
作者:
Shimono Y;Zabala M;Cho RW;Lobo N;Dalerba P;Qian D;Diehn M;Liu H;Panula SP;Chiao E;Dirbas FM;Somlo G;Pera RA;Lao K;Clarke MF

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Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and non-tumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429 and miR-183-96-182 were down-regulated in human BCSCs, normal human and murine mammary stem/progenitor cells and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. MiR-200c inhibited the clonogenicity of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated down-regulation of three microRNA clusters and the similar functional regulation of clonogenicity by miR-200c provide a molecular link that connects breast cancer stem cells with normal stem cells.
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