Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer |
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Authors: | Wei Zhang Jian He Yan Du Xian-Hua Gao Yan Liu Qi-Zhi Liu Wen-Jun Chang Guang-Wen Cao Chuan-Gang Fu |
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Affiliation: | Wei Zhang, Jian He, Xian-Hua Gao, Qi-Zhi Liu, Chuan-Gang Fu, Department of Colorectal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, ChinaYan Du, Yan Liu, Wen-Jun Chang, Guang-Wen Cao, Department of Epidemiology, The Second Military Medical University, Shanghai 200433, China |
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Abstract: | AIM: To investigate the expression and oncogenic role of nemo-like kinase(NLK) in colorectal cancer.METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer.RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer(P 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overallsurvival(hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P 0.001) and disease-free survival(hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. |
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Keywords: | Colorectal cancer Gene regulation Nemo-like kinase Prognosis |
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