Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Cancer Med. 2018 May;7(5):2048-2063. doi: 10.1002/cam4.1405. Epub 2018 Mar 23.
Laryngeal cancer is one of the most common head and neck malignant tumors and is commonly resistant to X-ray-based radiotherapy. NF-κB interacting lncRNA (NKILA) has been reported to serve as a tumor suppressor in several cancers through combining with NF-κB: IκB complex thereby inhibiting NF-κB 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-κB: IκB complex to inhibit IκB phosphorylation, inhibit p65 nuclear translocation, and finally inhibit NF-κB activation. NF-κB binds to the promoter region of NKILA to activate its transcriptional activity, upregulated NKILA then inhibits IκB phosphorylation and NF-κB 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.
喉癌是最常见的头颈部恶性肿瘤之一，通常对基于 X 射线的放射疗法有抗性。已经有报道称，NF-κB 相互作用的长非编码 RNA（NKILA）通过与 NF-κB：IκB 复合物结合来抑制 NF-κB 的激活，从而在几种癌症中充当肿瘤抑制因子。在此，我们证明了喉癌中 NKILA 的表达较低，并且与喉癌患者的总生存率较短相关。NKILA 通过抑制喉癌细胞活力和迁移，同时促进细胞凋亡，在喉癌中充当肿瘤抑制因子；而 NKILA 敲低通过与 NF-κB：IκB 复合物结合来抑制 IκB 磷酸化，抑制 p65 核易位，最终抑制 NF-κB 的激活，从而逆转 X 射线对喉癌细胞的细胞毒性。NF-κB 结合到 NKILA 的启动子区域以激活其转录活性，上调的 NKILA 随后抑制 IκB 磷酸化和 NF-κB 激活，从而形成负反馈环，使喉癌细胞对 X 射线辐射敏感。总之，NKILA 可以作为增强 X 射线辐射对喉癌细胞的细胞毒性并解决喉癌放射抗性的有前途的药物。
