A Cytoplasmic NF-kappa B Interacting Long Noncoding RNA Blocks I kappa B Phosphorylation and Suppresses Breast Cancer Metastasis

作者：Liu Bodu; Sun Lijuan; Liu Qiang; Gong Chang; Yao Yandan; Lv Xiaobin; Lin Ling; Yao Herui; Su Fengxi; Li Dangsheng; Zeng Musheng; Song Erwei^*

来源：Cancer Cell, 2015, 27(3): 370-381.

DOI：10.1016/j.ccell.2015.02.004

NF-kappa B 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-kappa B, binds to NF-kappa B/I kappa B, and directly masks phosphorylation motifs of I kappa B, thereby inhibiting IKK-induced I kappa B phosphorylation and NF-kappa B activation. Unlike DNA that is dissociated from NF-kappa B by I kappa B, NKILA interacts with NF-kappa B/I kappa B to form a stable complex. Importantly, NKILA is essential to prevent over-activation of NF-kappa B 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-kappa B modulators to suppress cancer metastasis.

• 单位
  1; 中国科学院上海生命科学研究院; 汕头大学; 中山大学