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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

    摘要
  • 摘要:
    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。

     

    Abstract:
    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.

     

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