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lncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance
Tao Yang1, Shisheng Li1, Jiajia Liu1
1Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Abstract:
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.
Insights
Low expression of NKILA (NF-κB interacting lncRNA) is linked to poor survival in laryngeal cancer. NKILA enhances radiotherapy effectiveness by inhibiting NF-κB activation, offering a potential strategy against radioresistance.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Laryngeal cancer is a common malignancy often resistant to radiotherapy.
- NF-κB interacting lncRNA (NKILA) functions as a tumor suppressor by inhibiting NF-κB activation.
- Understanding NKILA's role in laryngeal cancer is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate the expression levels and prognostic significance of NKILA in laryngeal cancer.
- To elucidate the mechanism by which NKILA influences laryngeal cancer cell behavior and radiosensitivity.
- To explore NKILA as a potential therapeutic target for overcoming radioresistance.
Main Methods:
- Quantitative analysis of NKILA expression in laryngeal cancer tissues.
- Correlation analysis between NKILA levels and patient overall survival.
- In vitro studies assessing the effects of NKILA modulation on cancer cell viability, migration, and apoptosis.
- Investigation of NKILA's interaction with the NF-κB signaling pathway components (IκB, p65) and its role in radiosensitization.
Main Results:
- NKILA expression was significantly lower in laryngeal cancer tissues compared to normal tissues.
- Low NKILA expression correlated with shorter overall survival in laryngeal cancer patients.
- NKILA suppressed laryngeal cancer cell viability and migration while promoting apoptosis.
- NKILA knockdown reversed the radiosensitizing effect of X-ray radiation by inhibiting the NF-κB pathway.
- A negative feedback loop exists where NF-κB activates NKILA transcription, and NKILA subsequently inhibits NF-κB activation.
Conclusions:
- NKILA acts as a tumor suppressor in laryngeal cancer.
- NKILA sensitizes laryngeal cancer cells to X-ray radiation by inhibiting the NF-κB pathway.
- NKILA represents a promising therapeutic target for enhancing radiotherapy efficacy and overcoming radioresistance in laryngeal cancer.
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