海南医学院学报2024，Vol.30Issue(19)：1468-1477,10.DOI:10.13210/j.cnki.jhmu.20240530.002
NKD1促进结肠癌细胞迁移的机制研究及临床意义
The mechanism of NKD1 promoting colon cancer cell migration and clinical significance
摘要
Abstract
Objective:To investigate the expression of NKD1 in colon cancer tissues and its correlation with clinicopathologic features in patients with colon cancer,and study the involvement of NKD1 in the migration of colon cancer cells and elucidate its precise mechanism in regulating the epithelial-mesenchymal transition(EMT)-related protein ZEB1.The findings of this study may contribute to the identification of novel therapeutic targets for metastatic colorectal cancer.Methods:Bioinformatics was used to analyze the expression of NKD1 in colon cancer cells and its correlation with clinical pathological characteristic factor.Through the collection of 98 pairs of colon cancer patient samples and relevant clinical information from Changzhou Wujin People's Hospi-tal,and after the verification of the bioinformatics results,the survival curve was drawn.Wound healing assay and Transwell assay were performed to prove that NKD1 promotes colon cancer cell migration.qPCR and Western lot experiments were used to con-firm that NKD1 regulates ZEB1 at the protein level.Western blot and immunoprecipitation experiments were conducted to further study the specific mechanism of NKD1 regulation of ZEB1.Results:NKD1 was highly expressed in colon cancer tissues,and its expression level was correlated with clinical characteristics such as differentiation,tumor staging,and whether there was distant metastasis or not.The high expression of NKD1 was associated with poor prognosis in colon cancer patients.The overexpression of NKD1 promoted the migration of colon cancer cells,while the knockdown of NKD1 led to the opposite result.NKD1 regulated EB1 at the protein level and could maintain the protein stability of ZEB1.The high expression of NKD1 inhibited the autophagy degradation of ZEB1 by regulating the binding of ZEB1 to autophagy related protein LC3.Conclusion:NKD1 is associated with poor prognosis in patients with colon cancer,and can inhibit autophagy degradation of ZEB1 by regulating the binding of ZEB1 to autophagy associated protein LC3,thus promoting the migration of colon cancer cells.关键词
结肠癌/NKD1/迁移/自噬Key words
Colon cancer/NKD1/Migration/Autophagy分类
医药卫生引用本文复制引用
陆玥瑶,邓建忠,刘迁,陆文斌..NKD1促进结肠癌细胞迁移的机制研究及临床意义[J].海南医学院学报,2024,30(19):1468-1477,10.基金项目
This study was supportecd by National Natural Science Foundation of China(81872275) （81872275）
Changzhou Sci&Tech Program(CJ20210015 （）
CJ20220006 （）
CJ20220007) （）
Innovation Team Project of the Science and Technology Development Fund at the Affiliated Hospital of Xuzhou Medical University(XYFC202303) 国家自然科学基金面上项目(81872275) （XYFC202303）
江苏省常州市科学技术局应用基础研究项目(CJ20210015 （）
CJ20220006 （）
CJ20220007) （）
徐州医科大学附属医院科技发展基金创新团队项目(XYFC202303) （XYFC202303）
