NKD1促进结肠癌细胞迁移的机制研究及临床意义OA北大核心CSTPCD
The mechanism of NKD1 promoting colon cancer cell migration and clinical significance
目的:探讨NKD1在结肠癌组织中的表达及其与结肠癌患者临床病理特征因素间的相关性,以及研究其在结肠癌细胞迁移中的作用,并明确其调控上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白ZEB1的具体机制,为转移性结肠癌提供新的治疗靶点.方法:使用生物信息学初步分析NKD1在结肠癌细胞中的表达情况及其与临床病理特征因素间的相关性.通过收集98对来自常州市武进人民医院的结肠癌患者组织样本及相关临床信息验证生物信息学结果,绘制生存曲线.划痕实验、Transwell实验证明NKD1 促进结肠癌细胞迁移.qPCR、western blot实验验证NKD1 在蛋白水平调控ZEB1.Western blot、免疫沉淀等实验深入研究NKD1调控ZEB1的具体机制.结果:NKD1在结肠癌组织中高表达,其表达水平与分化程度、肿瘤T分期及是否远处转移等临床病理特征因素具有相关性;NKD1高表达与结肠癌患者的不良预后相关;过表达NKD1后促进结肠癌细胞的迁移,敲除NKD1后则结果相反;NKD1在蛋白水平调控ZEB1,并能够维持ZEB1的蛋白稳定性;高表达NKD1通过调控ZEB1与自噬相关蛋白LC3的结合抑制ZEB1的自噬降解.结论:NKD1与结肠癌患者的不良预后相关,并且可以通过调控ZEB1与自噬相关蛋白LC3的结合抑制ZEB1的自噬降解,从而促进结肠癌细胞的迁移.
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.
陆玥瑶;邓建忠;刘迁;陆文斌
南京医科大学常州医学中心,常州市武进人民医院肿瘤科,江苏 常州 213017江苏大学附属武进医院,江苏 常州 213017||徐州医科大学武进临床学院,江苏 常州 213017||常州市分子诊断与肿瘤精准医学重点实验室,江苏 常州 213017||江苏大学武进分子诊断与肿瘤精准医学研究院,江苏 常州 213017南京医科大学常州医学中心,常州市武进人民医院肿瘤科,江苏 常州 213017||江苏大学附属武进医院,江苏 常州 213017||徐州医科大学武进临床学院,江苏 常州 213017||常州市分子诊断与肿瘤精准医学重点实验室,江苏 常州 213017||江苏大学武进分子诊断与肿瘤精准医学研究院,江苏 常州 213017
临床医学
结肠癌NKD1迁移自噬
Colon cancerNKD1MigrationAutophagy
《海南医学院学报》 2024 (019)
1468-1477 / 10
This study was supportecd by National Natural Science Foundation of China(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);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)
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