NKILA, a prognostic indicator, inhibits tumor metastasis by suppressing NF-κB/Slug mediated epithelial-mesenchymal transition in hepatocellular carcinoma
| Autor: | Kwabena Gyabaah Owusu-Ansah, Guangyuan Song, Shusen Zheng, Donghai Jiang, Qiyang Cheng, Ronggao Chen, Jian Wu, Lin Zhou, Xiao Xu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Carcinoma
Hepatocellular Epithelial-Mesenchymal Transition Slug Hepatocellular carcinoma Blotting Western Mice Nude Applied Microbiology and Biotechnology NF-κB Metastasis 03 medical and health sciences chemistry.chemical_compound In vivo Cell Line Tumor Medicine Animals Humans Epithelial–mesenchymal transition Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Cell Proliferation 0303 health sciences Epithelial to mesenchymal transition biology business.industry Liver Neoplasms NF-kappa B Cell Biology Middle Aged biology.organism_classification medicine.disease Prognosis Long non-coding RNA digestive system diseases LncRNA-NKILA IκBα chemistry Cancer research RNA Long Noncoding Snail Family Transcription Factors business Developmental Biology Signal Transduction Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | The metastasis of hepatocellular carcinoma (HCC) is one of the major obstacles hindering its therapeutic efficacy, leading to low surgical resection rate, high mortality and poor prognosis. Accumulating evidence has shown that both long noncoding RNA (lncRNA) and NF-κB play vital roles in the regulation of cancer metastasis. However, the clinical significance and biological function of NKILA (NF-κB interacting lncRNA) and its interaction with NF-κB in HCC remain unknown. In this study, we demonstrated that NKILA was down-regulated in HCC tissues and cell lines, and decreased NKILA expression was significantly associated with larger tumor size and positive vascular invasion in HCC patients. NKILA reduction was an independent risk factor of HCC patients' poor prognosis, and the 5-year overall survival (OS) rates of patients with low and high NKILA expression were 15.6% and 60.0%, respectively. Moreover, NKILA inhibits migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NKILA prevents Slug/epithelial to mesenchymal transition (EMT) pathway via suppressing phosphorylation of IκBα, p65 nuclear translocation and NF-κB activation. In conclusion, these results indicate that NKILA might serve as an effective prognostic biomarker and a promising therapeutic target against HCC metastasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|