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

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.

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

“…Besides, lowexpression of NKILA was statistically associated with advanced clinical staging, T classification and N classification in tongue squamous cell carcinoma patients. 18,19 Generally, NKILA low-expression predicts clinical progression and poor prognosis in most types of human tumors. In our study, we first showed NKILA lowexpression was obviously associated with advanced clinical stage (Ⅲ to Ⅳ stage), T classification (T3 to T4), N classification (N2), and N classification (M1) in rectal cancer patients.…”

“…15,16 Moreover, Yang et al 18 demonstrated that knockdown of NKILA expression promoted cell viability and migration, and reversed cell apoptosis F I G U R E 4 The molecular mechanism of NKILA in rectal cancer cell. We found NKILA overexpression dramatically repressed rectal cancer cell proliferation, migration, and invasion.…”

“…15,16 Moreover, Yang et al 18 demonstrated that knockdown of NKILA expression promoted cell viability and migration, and reversed cell apoptosis F I G U R E 4 The molecular mechanism of NKILA in rectal cancer cell. [14][15][16][17][18][19][20] In addition, NKILA was found to enhance the the anticancer effects of baicalein in hepatocellular carcinoma through modulating NF-κB signaling. B, NKILA overexpression inhibits p65 nuclear translocation and induces p65 cytoplasmic retention and the cytotoxicity of X-ray radiation.…”

Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma

“…Furthermore, as a transcription factor, NF-κB regulates expression of multiple downstream effectors, enhancing cell proliferation, inhibiting cell apoptosis, or promoting cell migration and invasion [32]. Herein, in NHL cells, down-regulation of NKILA resulted in increase of cellular proliferation and decrease of cell death, consistent with the tumor suppressor role of NKILA in multiple tumors, including melanoma, lung cancer, rectal cancer, laryngeal cancer and breast cancer [19,20,[33][34][35][36]. In addition, NKILA has also been shown to inhibit tumor invasion and migration in epithelial cancers, such as breast cancer, hepatocellular carcinoma and tongue squamous cell carcinoma [19,36,37].…”

Long non‑coding RNA NKILA serves as a biomarker in the early diagnosis and prognosis of patients with colorectal cancer

“…Nuclear factor (NF)-κB interacting long non-coding RNA (NKILA) was first reported to suppress the progression of breast cancer via its binding to NF-κB/inhibitor (I)κB and directly masking phosphorylation motifs of IκB, which inhibits IκB kinase-induced IκB phosphorylation and NF-κB activation (17). Further studies have demonstrated that NKILA suppresses the progression of malignant melanoma (18), non-small cell lung cancer (19), esophageal squamous cell carcinoma (20) and laryngeal cancer (21). Notably, NF-κB has been recognized as a critical factor in the initiation and progression of CRC (22)(23)(24).…”