lncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance

Laryngeal cancer is one of the most common head and neck malignant tumors and is commonly resistant to X-ray-based radiotherapy. NF-kappa B interacting lncRNA (NKILA) has been reported to serve as a tumor suppressor in several cancers through combining with NF-kappa B: I kappa B complex thereby inhibiting NF-kappa B activation. Herein, we demonstrated a low NKILA expression in laryngeal cancer and its correlation with shorter overall survival in patients with laryngeal cancer. NKILA serves as a tumor suppressor in laryngeal cancer by suppressing laryngeal cancer cell viability and migration, whereas promoting cell apoptosis; NKILA knockdown reverses the cytotoxicity of X-ray radiation on laryngeal cancer cells through combining with NF-kappa B: I kappa B complex to inhibit I kappa B phosphorylation, inhibit p65 nuclear translocation, and finally inhibit NF-kappa B activation. NF-kappa B binds to the promoter region of NKILA to activate its transcriptional activity, upregulated NKILA then inhibits I kappa B phosphorylation and NF-kappa B activation, thus forming a negative feedback loop to sensitize laryngeal cancer cell to X-ray radiation. In conclusion, NKILA can serve as a promising agent of enhancing the cytotoxicity of X-ray radiation on laryngeal cancer and addressing the radioresistance of laryngeal cancer.