MicroRNA-301 Mediates Proliferation and Invasion in Human Breast Cancer
MicroRNA-301 Mediates Proliferation and Invasion in Human Breast Cancer
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DOI：
10.1158/0008-5472.can-10-3369
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发表时间：
2011-04-15
期刊：
影响因子：
11.2
通讯作者：
Liu, Fei-Fei
中科院分区：
文献类型：
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作者：
Shi, Wei;Gerster, Kate;Liu, Fei-Fei
一些微小rna与人类乳腺癌有关，但迄今为止没有一个在临床管理中得到验证或持续使用。MicroRNA-301 （miR-301）过表达被认为是淋巴结阴性（LNN）浸润性导管乳腺癌的一个阴性预后指标，但其潜在的功能影响尚未确定。在乳腺癌细胞中，miR-301衰减降低了细胞增殖、克隆性、迁移、侵袭、他莫昔芬耐药性、肿瘤生长和微血管密度，确立了该基因的重要致癌作用。基于算法和实验的策略确定了FOXF2、BBC3、PTEN和COL2A1作为miR-301的候选靶点，所有这些靶点都通过荧光素酶报告基因检测证实为直接靶点。我们注意到miR-301位于SKA2基因的一个内含子中，SKA2基因负责着丝粒组装，并且发现这两个基因在原发性乳腺癌样本中共表达。总之，我们的研究结果确定miR-301在人类乳腺癌中是一个重要的致癌基因，通过多种途径和机制促进淋巴结或远处复发。癌症Res;71 (8);2926 - 37。AACR (C) 2011。
Several microRNAs have been implicated in human breast cancer but none to date have been validated or utilized consistently in clinical management. MicroRNA-301 (miR-301) overexpression has been implicated as a negative prognostic indicator in lymph node negative (LNN) invasive ductal breast cancer, but its potential functional impact has not been determined. Here we report that in breast cancer cells, miR-301 attenuation decreased cell proliferation, clonogenicity, migration, invasion, tamoxifen resistance, tumor growth, and microvessel density, establishing an important oncogenic role for this gene. Algorithm-based and experimental strategies identified FOXF2, BBC3, PTEN, and COL2A1 as candidate miR-301 targets, all of which were verified as direct targets through luciferase reporter assays. We noted that miR-301 is located in an intron of the SKA2 gene which is responsible for kinetochore assembly, and both genes were found to be coexpressed in primary breast cancer samples. In summary, our findings define miR-301 as a crucial oncogene in human breast cancer that acts through multiple pathways and mechanisms to promote nodal or distant relapses. Cancer Res; 71(8); 2926-37. (C)2011 AACR.