中国科学家发现遏制乳腺癌进展的重要microRNA
中国科学家发现遏制乳腺癌进展的重要microRNA来源：生物谷 2016-01-13 16:48http://cache1.bioon.com/fckup/2016/1/pharmon201601130959301121.jpg 2016年1月13日讯 /生物谷BIOON/ --许多研究表明转录因子NF-kB（nuclear factor kappa B）在肿瘤细胞中存在异常激活，是导致许多肿瘤发生的一个重要驱动因素。在正常的生理条件下，NF-kB信号的表达强度和持续时间会在多个水平上得到严格调控，但NF-kB信号途径在癌症中持续激活的机制究竟是什么一直没有得到完全阐述。
最近来自广州中山大学的研究人员在国际学术期刊cancer research上发表了一项最新研究进展，他们发现了一种microRNA发生沉默可能参与癌细胞内NF-kB信号的异常激活。
在这项研究中，研究人员在乳腺癌细胞中研究了microRNA介导的NF-kB信号级联调控，并发现miR-892b表达在人类乳腺癌标本中显著下调，同时该microRNA的表达情况与病人生存期存在相关性。
研究人员通过体外实验和体内实验证明，在乳腺癌细胞中过表达miR-892b能够显著抑制肿瘤细胞生长，转移能力以及诱导血管生成的能力，而删除细胞中的miR-892b则会增强上述特性。实验表明miR-892b能够通过直接靶向抑制NF-kB的多个调节蛋白的表达，抑制NF-kB信号途径，其靶向目标包括TRAF2, TAK1以及TAB3，因此乳腺癌细胞中的miR-892b发生沉默会维持NF-kB活性，导致该信号通路持续激活，进而增强肿瘤细胞生长和转移能力。
研究人员还发现miR-892b下调主要是由于其启动子发生高度甲基化所导致。
这项研究为深入理解乳腺癌细胞中NF-kB途径持续激活的机制提供了深入见解，同时研究结果还表明microRNA-892b具有肿瘤抑制功能，为未来开发microRNA类似物进行癌症治疗提供了新的基础。（生物谷Bioon.com）
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doi: 10.1158/0008-5472.CAN-15-1770
miR-892b silencing activates NF-κB and promotes aggressiveness in breast cancer
Lili Jiang1, Liang Yu2, Xin Zhang3, Fangyong Lei3, Lan Wang4, Xiangxia Liu5, Shu Wu6, Jinrong Zhu7, Geyan Wu8, Lixue Cao9, Aibin Liu10, Libing Song3,*, and Jun Li
The strength and duration of nuclear factor-kappa B (NF-κB) signaling is tightly controlled at multiple levels under physiological conditions, but the mechanism underlying constitutive activation of the NF-κB pathway in cancer remains unclear. In this study, we investigated micoRNA-mediated regulation of the NF-κB cascade in breast cancer. We report that miR-892b expression was significantly downregulated in human breast cancer specimens and correlated with poor patient survival. Overexpression of miR-892b in breast cancer cells significantly decreased tumor growth, metastatic capacity, and the ability to induce angiogenesis, whereas miR-892b depletion enhanced these properties, in vitro and in vivo. Furthermore, we demonstrate that miR-892b attenuated NF-κB signaling by directly targeting and suppressing multiple mediators of NF-κB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-κB activity. Moreover, miR-892b downregulation was attributed to aberrant hypermethylation of its promoter. Taken together, our results provide insight into a new mechanism by which NF-κB signaling becomes constitutively activated in breast cancer and suggest a tumor-suppressive role for miR-829b, prompting further investigation into microRNA mimics for cancer therapy.
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