let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells

详细信息    查看全文

• 作者：Fengyan Yu ; Herui Yao ; Pengcheng Zhu ; Xiaoqin Zhang ; Qiuhui Pan ; Chang Gong ; Yijun Huang ; Xiaoqu Hu ; Fengxi Su ; Judy Lieberman ; Erwei Song
• 关键词：STEMCELL ; HUMDISEASE
• 刊名：Cell
• 出版年：2007
• 出版时间：14 December 2007
• 年：2007
• 卷：131
• 期：6
• 页码：1109-1123
• 全文大小：2035 K

文摘

Cancers may arise from rare self-renewing tumor-initiating cells (T-IC). However, how T-IC self renewal, multipotent differentiation, and tumorigenicity are maintained remains obscure. Because miRNAs can regulate cell-fate decisions, we compared miRNA expression in self-renewing and differentiated cells from breast cancer lines and in breast T-IC (BT-IC) and non-BT-IC from 1° breast cancers. let-7 miRNAs were markedly reduced in BT-IC and increased with differentiation. Infecting BT-IC with let-7-lentivirus reduced proliferation, mammosphere formation, and the proportion of undifferentiated cells in vitro and tumor formation and metastasis in NOD/SCID mice, while antagonizing let-7 by antisense oligonucleotides enhanced in vitro self renewal of non-T-IC. Increased let-7 paralleled reduced H-RAS and HMGA2, known let-7 targets. Silencing H-RAS in a BT-IC-enriched cell line reduced self renewal but had no effect on differentiation, while silencing HMGA2 enhanced differentiation but did not affect self renewal. Therefore let-7 regulates multiple BT-IC stem cell-like properties by silencing more than one target.