BMP-6 inhibits cell proliferation by targeting microRNA-192 in breast cancer
BMP-6 inhibits cell proliferation by targeting microRNA-192 in breast cancer
复制标题
BMP-6 通过靶向乳腺癌中的 microRNA-192 抑制细胞增殖。
DOI：
10.1016/j.bbadis.2013.08.011
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发表时间：
2013-12-01
影响因子：
6.2
通讯作者：
Yang, Shuang
中科院分区：
文献类型：
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作者：
Hu, Fen;Meng, Xiangzhi;Yang, Shuang
尽管骨形态发生蛋白-6 （BMP-6）已被确定为与乳腺癌分化和转移相关的肿瘤抑制因子，但BMP-6在调节细胞周期进程中的潜在作用尚未得到充分研究。在本研究中，我们提供了新的发现，诱导BMP-6在。在裸鼠异种移植瘤模型中，MDA-MB-231乳腺癌细胞通过减少细胞周期S期的细胞数量，显著抑制细胞增殖，从而抑制肿瘤发生。进一步研究表明，BMP-6上调MDA-MB-231细胞中microRNA-192 （miR-192）的表达。miR-192表达升高导致细胞生长停滞，这与BMP-6诱导的效果相似。重要的是，通过miRNA抑制内源性miR-192的消耗显著减弱了bmp -6介导的细胞周期进程的抑制。在乳腺癌组织中，肿瘤样本中miR-192的表达显著下调，且与BMP-6的表达呈正相关，说明BMP-6通过调控miR-192对细胞增殖有抑制作用。此外，使用RT2 Profiler PCR阵列，视网膜母细胞瘤1 （RB1）被确定为BMP-6/miR-192通路调节乳腺癌细胞增殖的直接靶点。总之，我们已经确定了BMP-6/miR-192信号在乳腺癌细胞周期进程调节中的重要作用。此外，BMP-6/miR-192在乳腺癌标本中低水平表达，表明该途径可能是乳腺癌治疗的一个有希望的治疗靶点。(C) 2013 Elsevier B.V.版权所有
Although bone morphogenetic protein-6 (BMP-6) has been identified as a tumor suppressor associated with breast cancer differentiation and metastasis, the potential roles of BMP-6 in regulating cell cycle progression have not been fully examined. In the present study, we provide the novel finding that induction of BMP-6 in. MDA-MB-231 breast cancer cells significantly inhibits cell proliferation by decreasing the number of cells in S phase of the cell cycle, resulting in inhibition of tumorigenesis in a nude mouse xenograft model. Further investigation indicated that BMP-6 up-regulates the expression of microRNA-192 (miR-192) in MDA-MB-231 cells. Elevated expression of miR-192 caused cell growth arrest, which is similar to the effect of BMP-6 induction. Importantly, depletion of endogenous miR-192 by miRNA inhibition significantly attenuated BMP-6-mediated repression of cell cycle progression. In breast cancer tissue, miR-192 expression is significantly down-regulated in tumor samples and positively correlates with the expression of BMP-6, demonstrating the inhibitory effect of BMP-6 on cell proliferation through miR-192 regulation. Additionally, using the RT2 Profiler PCR Array, retinoblastoma 1 (RB1) was identified as a direct target of the BMP-6/miR-192 pathway in regulating cell proliferation in breast cancer. In conclusion, we have identified an important role for BMP-6/miR-192 signaling in the regulation of cell cycle progression in breast cancer. Furthermore, BMP-6/miR-192 was expressed at low levels in breast cancer specimens, indicating that this pathway might represent a promising therapeutic target for breast cancer treatment. (C) 2013 Elsevier B.V. All rights reserved.