Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Gene Engineering of Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Cancer Cell. 2015 Mar 9;27(3):370-81. doi: 10.1016/j.ccell.2015.02.004.
NF-κB is a critical link between inflammation and cancer, but whether long non-coding RNAs (lncRNAs) regulate its activation remains unknown. Here, we identify an NF-KappaB Interacting LncRNA (NKILA), which is upregulated by NF-κB, binds to NF-κB/IκB, and directly masks phosphorylation motifs of IκB, thereby inhibiting IKK-induced IκB phosphorylation and NF-κB activation. Unlike DNA that is dissociated from NF-κB by IκB, NKILA interacts with NF-κB/IκB to form a stable complex. Importantly, NKILA is essential to prevent over-activation of NF-κB pathway in inflammation-stimulated breast epithelial cells. Furthermore, low NKILA expression is associated with breast cancer metastasis and poor patient prognosis. Therefore, lncRNAs can directly interact with functional domains of signaling proteins, serving as a class of NF-κB modulators to suppress cancer metastasis.
NF-κB 是炎症和癌症之间的关键环节，但长非编码 RNA（lncRNA）是否调节其激活尚不清楚。在这里，我们鉴定了一种 NF-κB 相互作用的 lncRNA（NKILA），它受 NF-κB 上调，与 NF-κB/IκB 结合，并直接掩盖 IκB 的磷酸化基序，从而抑制 IKK 诱导的 IκB 磷酸化和 NF-κB 激活。与 IκB 从 NF-κB 解离的 DNA 不同，NKILA 与 NF-κB/IκB 相互作用形成稳定的复合物。重要的是，NKILA 对于防止炎症刺激的乳腺上皮细胞中 NF-κB 途径的过度激活是必不可少的。此外，NKILA 表达水平低与乳腺癌转移和患者预后不良有关。因此，lncRNA 可以直接与信号蛋白的功能域相互作用，作为一类 NF-κB 调节剂抑制癌症转移。
