LncSox4在非小细胞肺癌中的表达及生物学作用

Expression and biological role of LncSox4 in non-small cell lung cancer

目的检测LncSox4在人非小细胞肺癌(NSCLC)中的表达水平变化,初步探讨其生物学作用及机制,为NSCLC诊断和治疗提供新的生物指标。方法采用qRT-PCR检测LncSox4在NSCLC患者肿瘤组织中的表达水平。通过克隆形成试验、生长曲线分析、Transwell迁移和侵袭试验检测敲除LncSox4对A549细胞生物学功能的影响;采用流式细胞术分析细胞周期情况;采用qRT-PCR和western blot检测上皮-间质转化(EMT)相关基因及蛋白质的表达水平。结果与癌旁对照相比,LncSox4在NSCLC癌组织中呈显著高表达(t=7.109,P<0.01);LncSox4基因沉默后,A549细胞生长速度减缓,细胞克隆形成数量减少(P<0.01),细胞迁移和侵袭能力降低(P<0.01),诱导细胞发生G 1期阻滞(P<0.01);LncSox4基因沉默抑制A549细胞中Cyclin D1、c-Myc、N-cadherin、Vimentin蛋白的表达,促进E-cadherin蛋白的表达;LncSox4基因沉默还显著降低EMT相关转录因子Snail、Slug和Twist的表达水平。结论LncSox4在NSCLC中高表达,通过影响细胞增殖、迁移和侵袭促进NSCLC恶性进展,有望成为NSCLC诊疗新靶点。

Objective To determine the changed expression levels,biological roles and underlying mechanism of LncSox4 in non-small cell lung cancer(NSCLC),providing novel biomarkers for NSCLC diagnosis and therapy.Methods QRT-PCR was used to detect the expression of LncSox4 in the tumor tissues of NSCLC patients.Colony formation,cell growth curve,Transwell migration and invasion assays were used to determine the effects of LncSox4 knockdown on A549 cell function,respectively.Flow cytometry was used to determine the effects of LncSox4 on the progression of A549 cell cycle.QRT-PCR and western blot were used to explore the expressions of genes and proteins in epithelial-mesenchymal transition(EMT).Results The expression of LncSox4 was upregulated significantly in carcinoma tissues of NSCLC compared to the para-carcinoma tissues(t=7.109,P<0.01).The growth rate of A549 cells slowed down in LncSox4 knockdown group and the number of formed cell colonies was less than that in control group(P<0.01).LncSox4 knockdown reduced the migration and invasion abilities of A549 cells(P<0.01)and induced cell cycle arrest at G 1 phase(P<0.01).LncSox4 knockdown downregulated the protein expressions of Cyclin D1,c-Myc,N-cadherin,and Vimentin,while upregulated the expression of E-cadherin in A549 cells.LncSox4 knockdown also decreased the expressions of EMT-related transcription factors including snail,slug and twist.Conclusion The high expression of LncSox4 in NSCLC may promote malignant progression of NSCLC by enhancing cell proliferation,migration and invasion,suggesting that it should be a promising target for diagnosis and therapy of NSCLC.