HOXC8通过调控PDX1的表达促进非小细胞肺癌的生长与EMT过程

HOXC8 Regulates PDX1 Expression to Promote Growth and EMT of non-small Cell Lung Cancer

目的:探索HOXC8与PDX1在非小细胞肺癌(non-small lung cancer,NSCLC)细胞生长及上皮间质转化(Epithelial-mesenchymal transition,EMT)的作用机制。方法:通过转录组测序、荧光定量PCR及染色质免疫沉淀等方法筛选并鉴定HOXC8调控的靶基因;通过Western blot、CCK-8、克隆集落生成及生物信息学等手段分析靶基因PDX1在非小细胞肺癌中的作用。结果:实验证明HOXC8可结合到PDX1基因的启动子上,并作为转录因子激活PDX1的表达。PDX1的表达促进NSCLC细胞的生长与EMT过程,而沉默PDX1能显著地抑制NSCLC细胞的生长与EMT过程,并诱导细胞的凋亡。通过分析已知的肿瘤数据库,我们发现在NSCLC中PDX1的表达显著高于正常组织,且PDX1的高表达与肺癌患者的预后不良呈显著的相关性。结论:本研究发现HOXC8-PDX1轴在非小细胞肺癌中起着重要的调节作用,可有望成为非小细胞肺癌治疗的新靶点。

Objective:To investigate the regulation mechanism of HOXC8 and PDX1 in the growth and epithelial mesenchymal transition(EMT)of non-small lung cancer(NSCLC)cells.Methods:RNA-sequence analyses,Chromatin immunoprecipitation(ChIP)and Real-time PCR assays were performed to identify HOXC8-targeted genes;Western blot,CCK-8,colony formation and bioinformatics analyses were carried out to examine the roles of PDX1 gene in NSCLC.Results:HOXC8 was shown to bind to the promoter of the PDX1 gene and act as a transcription factor to activate the expression of PDX1.PDX1 expression promoted the growth and EMT of NSCLC cells,while silencing PDX1 significantly inhibited the growth and EMT of NSCLC,and induced cell apoptosis.PDX1 expression was significantly higher in NSCLC specimens than that of normal tissues by analyzing public tumor databases,and growth and EMT of NSCLC,and induced cell apoptosis.Analyses of public tumor databases indicated that PDX1 expression was significantly up-regulated in NSCLC specimens in comparison with normal tissues,and high PDX1 expression was significantly correlated with poor survival of lung cancer patients.Conclusion:This study showed that HOXC8-PDX1 axis played an important role in the progression of NSCLC and would be a new target for NSCLC treatment.