miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours
miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours
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DOI：
10.1002/emmm.201201483
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发表时间：
2012-11-01
影响因子：
11.1
通讯作者：
Blandino, Giovanni
中科院分区：
文献类型：
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作者：
Biagioni, Francesca;Ben-Moshe, Noa Bossel;Blandino, Giovanni
不受管制的增殖是癌细胞的标志。在这里，我们表明microRNA-10b*是乳腺癌细胞增殖的主要调节因子，与匹配的瘤周对应物相比，在肿瘤样本中下调。在分析的乳腺癌组织中，前体序列上游的两个典型的CpG岛(5kb)被高度甲基化。将合成的microRNA-10b*异位输送到乳腺癌细胞系或异种移植的小鼠乳腺肿瘤中，分别抑制细胞增殖和损害体内肿瘤的生长。我们在体外和体内鉴定并验证了miR-10b*的三个新的靶向mRNAs(Bub1、PLK1和Ccna2)，它们在细胞周期调节中起着显著的作用，与低表达的患者相比，它们在乳腺癌患者中的高表达与无瘤生存期、无复发生存期和无转移生存期的降低有关。这也表明，恢复microRNA-10b*的表达可能具有治疗前景。
Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5?kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise.