长链非编码RNA PCAT19通过负调控p53水平促进非小细胞肺癌细胞的增殖

Long-chain noncoding RNA PCAT19 promoting proliferation of non-small cell lung cancer cells by negatively regulating p53 level

目的检测长链非编码RNA PCAT19在非小细胞肺癌中的表达水平及对非小细胞肺癌进展的影响。方法收集2013年1月-2015年1月在我院接受手术治疗的NSCLC患者78例,男性52例,女性26例,年龄37-72岁,记录患者的一般临床资料;qRT-PCR检测非小细胞肺癌肿瘤组织、癌旁组织中PCAT19和p53 mRNA的相对表达水平,根据PCAT19 mRNA相对表达水平将患者分为PCAT19高表达组和低表达组;Kaplan-Meier法计算患者的生存率,log-rank比较PCAT19高表达组和低表达组患者的生存率;Pearson相关性分析NSCLC组织中PCAT19的表达水平与p53 mRNA的相关性;Western blot实验检测PCAT19和p53蛋白表达水平;细胞增殖实验检测各组细胞的增殖能力。结果 PCAT19在非小细胞肺癌组织中的平均表达水平显著高于癌旁组织(t=19.662,P<0.001),PCAT19高表达组55例,PCAT19低表达组23例,PCAT19高表达组与PCAT19低表达组患者在性别、年龄、病理类型和分化程度之间差异无统计学意义(P>0.05),在TNM分期和淋巴结转移之间有差异(P<0.05),且PCAT19高表达组患者的5年生存率显著低于PCAT19低表达组(HR=1.866,95%CI:1.020-3.414,P=0.043);非小细胞肺癌组织中PCAT19的表达水平与p53 mRNA水平呈负相关(r=-0.279,P=0.014);PCAT19组p53 mRNA水平1.51±0.18与对照组2.7±0.16相比显著降低(q=13.221,P<0.001),PCAT19-siRNA组p53 mRNA 3.28±0.16与对照组2.70±0.16相比显著增加(q=6.831,P=0.009);PCAT19组细胞的增殖能力强于对照组和阴性对照组,PCAT19-siRNA组细胞的增殖能力弱于对照组和阴性对照组,PCAT19+p53组与PCAT19组相比细胞的增殖能力减弱。结论 PCAT19通过负调控p53肿瘤抑制途径,促进非小细胞肺癌细胞的增殖,与肿瘤的分期和淋巴结转移有关。

Objective To detect the expression of non-coding RNA PCAT19 in non-small cell lung cancer and its effect on the progression of non-small cell lung cancer.Methods A total of 78 patients with NSCLC who underwent surgical treatment in our hospital from January 2013 to January 2015 were collected,52 males and 26 females,aging from 37-72 years old,and their general clinical data were recorded.qRT-PCR was used to detect the expression levels of PCAT19 and p53 mRNA in non-small cell lung cancer tumor tissues and adjacent tissues.The patients were divided into the PCAT19 high expression group and the low expression group according to the relative expression level of PCAT19 mRNA.Kaplan-Meier method was used to calculate the survival rate of patients,and log-rank was used to compare the survival rates of patients with high and low expression in the PCAT19 group.Pearson correlation analysis was used to analyze the correlation between PCAT19 expression level and p53 mRNA in NSCLC tissues.Western blot was used to detect the expression of PCAT19 and p53 protein.Cell proliferation was used to detect the proliferation of cells in each group.Results The average expression level of PCAT19 in non-small cell lung cancer tissues was significantly higher than that in adjacent tissues(t=19.662,P<0.001).There were 55 cases in the PCAT19 high expression group and 23 cases in the PCAT19 low expression group.There was no significant difference in gender,age,pathological type,and degree of differentiation between the PCAT19 high-expression group and the PCAT19 low-expression group(P>0.05),and there was a difference between TNM staging and lymph nodemetastasis(P<0.05).The 5-year survival rate of the PCAT19 high expression group was significantly lower than that of the PCAT19 low expression group(HR=1.866,95%CI:1.020-3.414,P=0.043).The expression level of PCAT19 in non-small cell lung cancer tissues was negatively correlated with the level of p53 mRNA(r=-0.279,P=0.014).The p53 mRNA level of the PCAT19 group was 1.51±0.18 significantly lower than that of the control group(2.7±0.16,q=13.221,P<0.001).The level of p53 mRNA in the PCAT19-siRNA group(3.28±0.16)was significantly increased while compared with the control group(2.70±0.16,q=6.831,P=0.009).The cell proliferation ability of the PCAT19 group was stronger than that of the control group and the negative control group.The cell proliferation ability of the PCAT19-siRNA group was weaker than that of the control group and the negative control group.The proliferation ability of the PCAT19+p53 group was weaker than that of the PCAT19 group.Conclusion PCAT19 can promote the proliferation of non-small cell lung cancer cells by negatively regulating the p53 tumor suppressor pathway,which is related to tumor stage and lymph node metastasis.