透明细胞肾细胞癌中FOXD1的表达及其对786-O细胞增殖侵袭、上皮-间质转化的影响

Expression of FOXD1 in renal clear cell carcinoma and its effect on proliferation,invasion and EMT of 786-O cells

目的探讨转录因子FOXD1在透明细胞肾细胞癌(clear cell renal cell carcinoma,CCRCC)组织和细胞系中的表达及其对786-O细胞增殖侵袭、上皮-间质转化(epithelial-mesenchymal transition,EMT)的影响。方法采用qRT-PCR技术检测CCRCC组织和细胞系中FOXD1基因表达,并分析FOXD1表达与CCRCC临床病理特征及预后的关系;检测敲低FOXD1表达对786-O细胞生物学行为和EMT相关标志物表达的影响。结果CCRCC组织中FOXD1的表达量(0.9172±0.09658)高于对照组(0.5569±0.07482),差异有统计学意义(P<0.05)。肿瘤TNM分期、淋巴结转移及FOXD1高表达均为CCRCC患者预后相关的独立危险因子(P<0.05)。下调FOXD1基因发现,CCRCC细胞系786-O的体外侵袭与增殖活性明显减弱(P<0.05)。与对照组相比,敲低FOXD1表达后N-cadherin、Ki-67和vimentin表达下调(P<0.05),E-cadherin表达上调(P<0.05),差异均有统计学意义。结论FOXD1在CCRCC中异常高表达是影响CCRCC患者预后的独立因素,沉默FOXD1可使786-O细胞的增殖侵袭活性减弱,并抑制EMT进程,FOXD1发挥促癌基因作用。

Purpose To investigate the expression of transcription factor FOXD1 in clear cell renal cell carcinoma(CCRCC)tissues and cell lines and its effect on the proliferation,invasion and epithelial-mesenchymal transition(EMT)of 786-O cells.Methods The mRNA expression of FOXD1 in CCRCC tissues and cell lines was detected by qRT-PCR,and the relationship between FOXD1 expression and the clinicopathological features and prognosis of CCRCC was analyzed.After down-regulating FOXD1 expression,the effects on the biological behavior of 786-O cells and the expression of EMT-related markers were detected.Results The mRNA expression of FOXD1 in CCRCC tissues(0.9172±0.09658)was significantly higher than that in adjacent normal tissues(0.5569±0.07482,P<0.05).TNM stage,lymph node metastasis and high expression of FOXD1 were independent prognostic factors of CCRCC patients(P<0.05).Down-regulation of FOXD1 significantly attenuated the invasion and proliferation activities of 786-O cells in vitro(P<0.05).FOXD1 down-regulated the expression of N-cadherin,Ki-67 and vimentin(P<0.05),but significantly increased the expression of E-cadherin(P<0.05).Conclusion Abnormally high expression of FOXD1 in CCRCC is an independent prognostic factor for CCRCC patients.Down-regulating FOXD1 expression can attenuate the proliferation and invasion activity of CCRCC,inhibit the process of EMT,and play a role of oncogene.