2016年1月13日訊 /生物谷BIOON/ --許多研究表明轉錄因子NF-kB（nuclear factor kappa B）在腫瘤細胞中存在異常激活，是導致許多腫瘤發生的一個重要驅動因素。在正常的生理條件下，NF-kB信號的表達強度和持續時間會在多個水平上得到嚴格調控，但NF-kB信號途徑在癌症中持續激活的機制究竟是什麼一直沒有得到完全闡述。
最近來自廣州中山大學的研究人員在國際學術期刊cancer research上發表了一項最新研究進展，他們發現了一種microRNA發生沉默可能參與癌細胞內NF-kB信號的異常激活。
在這項研究中，研究人員在乳腺癌細胞中研究了microRNA介導的NF-kB信號級聯調控，並發現miR-892b表達在人類乳腺癌標本中顯著下調，同時該microRNA的表達情況與病人生存期存在相關性。
研究人員通過體外實驗和體內實驗證明，在乳腺癌細胞中過表達miR-892b能夠顯著抑制腫瘤細胞生長，轉移能力以及誘導血管生成的能力，而刪除細胞中的miR-892b則會增強上述特性。實驗表明miR-892b能夠通過直接靶向抑制NF-kB的多個調節蛋白的表達，抑制NF-kB信號途徑，其靶向目標包括TRAF2, TAK1以及TAB3，因此乳腺癌細胞中的miR-892b發生沉默會維持NF-kB活性，導致該信號通路持續激活，進而增強腫瘤細胞生長和轉移能力。
研究人員還發現miR-892b下調主要是由於其啟動子發生高度甲基化所導致。
這項研究為深入理解乳腺癌細胞中NF-kB途徑持續激活的機制提供了深入見解，同時研究結果還表明microRNA-892b具有腫瘤抑制功能，為未來開發microRNA類似物進行癌症治療提供了新的基礎。（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.