A Cytoplasmic NF-κB Interacting Long Noncoding RNA Blocks IκB Phosphorylation and Suppresses Breast Cancer Metastasis

• NF-κB interacting long noncoding RNA (NKILA) directly blocks IκB phosphorylation
• NKILA interacts with NF-κB/IκB to form a stable ternary complex
• NKILA is a negative feedback regulator of NF-κB in both resting and activated cells
• Decreased NKILA in invasive breast cancer is associated with poor patient outcome

SummaryNF-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.

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