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Published on: January 18, 2017
NKILA inhibits NF-κB signaling and suppresses tumor metastasis
Shun Ke1, Rui-Chao Li2, Fan-Kai Meng3
1Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Abstract:
The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-κB interacting lncRNA) functions as a suppressor in human breast cancer and tongue cancer. However, the clinical significance and biological roles of NKILA in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we showed that NKILA was downregulated in ESCC tissues and cancer cells compared with their normal counterparts. Low NKILA expression correlated with large tumor size and advanced TNM stage, and predicted poor overall and disease-free survival of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA inhibited proliferation and migration of ESCC cells in vitro, suppressed tumor growth and lung metastasis in vivo. Mechanistically, NKILA could inhibit phosphorylation of IκBα, suppress p65 nuclear translocation and downregulate the expression of NF-κB target genes in ESCC cells. These results suggest NKILA could suppress malignant development of ESCC via abrogation of the NF-κB signaling and may potentially serve as a prognostic marker for ESCC.
Insights
The long non-coding RNA NKILA suppresses esophageal squamous cell carcinoma (ESCC) by inhibiting the NF-κB pathway. Lower NKILA levels indicate poorer patient survival, suggesting its potential as a prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in cancer.
- NKILA (nuclear transcription factor NF-κB interacting lncRNA) is a known tumor suppressor in breast and tongue cancers.
- The role of NKILA in esophageal squamous cell carcinoma (ESCC) is currently unknown.
Purpose of the Study:
- To investigate the clinical significance and biological functions of NKILA in ESCC.
- To elucidate the underlying molecular mechanisms of NKILA's action in ESCC.
- To evaluate NKILA as a potential prognostic biomarker for ESCC patients.
Main Methods:
- Analysis of NKILA expression in ESCC tissues and cell lines.
- Correlation analysis between NKILA expression and clinicopathological features.
- In vitro and in vivo loss- and gain-of-function assays to assess NKILA's effects on cell proliferation, migration, tumor growth, and metastasis.
- Investigation of NKILA's impact on the NF-κB signaling pathway.
Main Results:
- NKILA expression was significantly downregulated in ESCC tissues and cells.
- Low NKILA expression correlated with larger tumor size, advanced TNM stage, and poorer patient survival.
- NKILA inhibited ESCC cell proliferation and migration in vitro, and suppressed tumor growth and lung metastasis in vivo.
- NKILA abrogated NF-κB signaling by inhibiting IκBα phosphorylation, p65 nuclear translocation, and NF-κB target gene expression.
Conclusions:
- NKILA acts as a tumor suppressor in ESCC by inhibiting the NF-κB signaling pathway.
- NKILA downregulation is associated with malignant progression and poor prognosis in ESCC.
- NKILA holds potential as a valuable prognostic marker for ESCC.
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