APOBEC3B介导的p53突变在NSCLC转移中的作用

Effect of p53 mutation mediated by APOBEC3B on NSCLC metastasis

目的 APOBEC3B(A3B)是载脂蛋白B mRNA编辑酶催化多肽(APOBEC)家族的重要成员,本课题旨在研究其在非小细胞肺癌(NSCLC)转移的重要作用。方法分析249例NSCLC组织中A3B表达与临床病理资料的统计学关系,Sanger测序法检测其中74例肺癌组织中p53第5、6、7、8号外显子突变情况,并在人肺腺癌细胞HCC827细胞中构建A3B过表达细胞系,观察细胞迁移能力的改变。结果与正常肺组织比较,A3B在NSCLC组织中高表达(P <0. 01),其表达与NSCLC淋巴结转移密切相关,且p53突变率与A3B表达呈正相关。体外实验发现,过表达A3B后细胞迁移能力增强,转移潜能增加。结论 A3B介导的p53突变可能在NSCLC转移中具有关键作用。

Objective APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family. This study aimed to investigate its important role in the metastasis of small cell lung cancer (NSCLC). Methods The statistical relationship between A3B and clinicopathological data was analyzed in 249 cases of NSCLC. Sanger sequencing was used to detect mutations in exon 5, 6, 7 and 8 of P53 in 74 cases of lung cancer. A3B overexpression cell line was constructed in human lung adenocarcinoma cells HCC827 to observe the change of cell migration and metastasis capacity. Results A3B was highly expressed in NSCLC tissues compared with normal lung tissues. The expression of A3B was closely related to the lymph node metastasis of NSCLC and the mutation rate of p53 was positively correlated with the expression of A3B. In vitro experiment, it showed enhanced migration and increased metastatic potential in cells after overexpression of A3B. Conclusions A3B-mediated mutations in P53 may play a key role in the metastasis of NSCLC.