PROX1通过上皮间质转化促进非小细胞肺癌进展

PROX1 promoted the progression of non-small cell lung cancer via epithelial-mesenchymal transition

目的:探讨转录因子Prospero同源框1(Prospero-related homeobox 1,PROX1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)进展中的作用和机制。方法:对含有108对非小细胞肺癌组织的组织芯片进行免疫组化染色,分析PROX1表达和NSCLC患者预后间的关系。采用Western印迹法和实时定量PCR分析PROX1在NSCLC细胞系中的表达情况和上皮间质转化的标志物。采用CCK-8、Transwell试验检测肿瘤细胞的增殖、迁移和侵袭能力。结果:PROX1在非小细胞肺癌组织中的表达上调。PROX1的表达与肿瘤直径、淋巴转移显著相关(P=0.003、0.042)。高表达PROX1的NSCLC患者其5年复发率高于PROX1低表达组(70.9%vs 50.9%,P=0.005),而5年生存率低于PROX1低表达组(49.1%vs 66.0%,P=0.016)。CCK-8和Transwell实验的结果显示,敲减PROX1后肿瘤的增殖、侵袭和转移能力明显减弱(P<0.01、P<0.05)。敲减PROX1后E-钙粘蛋白表达上调而波形蛋白表达下降(P<0.001)。结论:PROX1表达增高可通过促进上皮间质转化而促进NSCLC进展;PROX1是潜在的NSCLC预后预测因子。

Objective:To explore the function and mechanism of PROX1 in non-small cell lung cancer(NSCLC).Methods:The tissue micro-array containing 108 NSCLC tissues was used to explore the relationship between the expression of PROX1 and the prognosis of NSCLC patients.Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the expression of PROX1 in the NSCLC cell line and detect the biomarkers of epithelial-to-mesenchymal transition(EMT).Moreover,the CCK8 and Transwell assay was used to detect the proliferation,invasion,and migration ability of the NSCLC cell line.Results:The expression of PROX1 was upregulated in NSCLC.The expression of PROX1 was closely associated with tumor size and lymphocyte metastasis(P=0.003 and 0.042).The NSCLC patients in the PROX1 high group had a higher recurrence rate and lower survival rate than in the PROX1 low group with the five-year recurrence rate(70.9%vs 50.9%,P=0.005)and the five-year survival rate(49.1%vs 66%,P=0.016).The CCK-8 and Transwell assays showed that the proliferation,invasion,and migration of NSCLC were significantly reduced after the knockdown of PROX1(P<0.01、P<0.05).In terms of mechanism,the knockdown of PROX1 led to the upregulation of E-cadherin and reduction of vimentin(P<0.001).Conclusions:The upregulation of PROX1 contributes to the progression of NSCLC through EMT and it can be a potential biomarker for the prognosis of NSCLC.