转录因子KLF12在非小细胞肺癌中的表达及其对PD-L1的调控机制

The Expression of Transcription Factor KLF12 in Non-small Cell Lung Cancer and Its Regulatory Mechanism on PD-L1

目的探究Krüppel样因子12(KLF12)在非小细胞肺癌(NSCLC)中表达及其对程序性死亡因子配体1(PD-L1)的调控机制。方法收集2017年5月至2019年5月福建医科大学附属宁德市医院收治的87例NSCLC患者的癌组织及癌旁正常组织标本用于本研究,采用免疫组化染色法检测KLF12和PD-L1蛋白在NSCLC组织及癌旁正常组织中的表达水平,分析KLF12、PD-L1表达与NSCLC患者临床病理特征的关系,采用Spearman相关分析NSCLC患者中KLF12、PD-L1表达的相关性。将人非小细胞肺癌细胞NCI-H1299分为siRNA-NC组(转染KLF12-siRNA)和siRNA-KLF12组(转染无关干扰序列),采用qRT-PCR检测两组KLF12、PD-L1 mRNA表达水平,采用Western blot检测两组KLF12、PD-L1蛋白表达水平。结果KLF12和PD-L1蛋白在NSCLC组织中阳性表达率显著低于癌旁正常组织(P<0.05);TNM分期不同的NSCLC患者癌组织中KLF12、PD-L1表达水平差异具有统计学意义(P<0.05);KLF12与PD-L1在非小细胞肺癌中的表达呈正相关(P<0.05);siRNA-KLF12组KLF12、PD-L1 mRNA及蛋白表达水平较siRNA-NC组明显下降(P<0.05)。结论KLF12、PD-L1在非小细胞肺癌中表达水平均呈下降趋势,PD-L1表达受KLF12调控,KLF12可能通过促进PD-L1转录从而增加其表达,有望成为抗非小细胞肺癌的新治疗靶点。

Objective To investigate the expression of transcription factor Krüppel-like factor 12(KLF12)in non-small cell lung cancer(NSCLC)and its regulatory mechanism on programmed death ligand-1(PD-L1).Methods In the current study,the expression levels of KLF12 and PD-L1 proteins in NSCLC cancer tissues and adjacent normal tissues collected in our hospital from May,2017 to May,2019 were detected by immunohistochemical staining,and their correlations with clinicopathological features were determined.Spearman correlation was used to analyze the correlation of KLF12 and PD-L1 expressions in NSCLC patients.Human non-small cell lung cancer cells NCI-H1299 were divided into the siRNA-NC group(KLF12-siRNA)and siRNA-KLF12 group(interference sequence),and received the corresponding treatments,then the mRNA and protein expression levels of KLF12 and PD-L1 were detected by qRT-PCR and western Blot.Results The positive expression rates of KLF12 and PD-L1 proteins in NSCLC tissues were significantly lower than those in adjacent normal tissues(P<0.05).The expression levels of KLF12 and PD-L1 in NSCLC patients with different TNM stages were significantly different(P<0.05).The expression of KLF12 and PD-L1 in NSCLC was positively correlated(P<0.05).The mRNA and protein expressions of KLF12 and PD-L1 in the siRNA-KLF12 group was significantly lower than those in the siRNA-NC group(P<0.05).Conclusion The expressions of KLF12 and PD-L1 in non-small cell lung cancer are down-regulated,and the expression of PD-L1 is regulated by KLF12.KLF12 may increase the expression of PD-L1 by promoting transcription of PD-L1,which is expected to become a novel therapeutic target for non-small cell lung cancer.