心脏高表达基因ZNF425在肺癌中功能的探究

Study on the Function of Heart High-expression Gene ZNF425 in Lung Cancer

为研究ZNF425与肺癌之间的关系,先利用生物信息学的方法研究ZNF425与肺癌的相关性。基于癌症和肿瘤基因图谱(TCGA)数据库、癌症和正常基因表达谱公共数据库(GEPIA)中ZNF425与肺癌两种亚型肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)的数据进行后期运算分析,发现在癌组织中ZNF425表达降低,这种现象在肺癌Ⅲ期尤为明显。同时数据显示ZNF425高表达患者生存率更高。再利用人类肺癌样本免疫组化证实了生物信息学的分析结果,与癌旁组织相比,Ⅰ,Ⅱ,Ⅲ期癌症组织中的ZNF425显著下调。最后,构建ZNF425过表达质粒在肺癌A549细胞系瞬时过表达ZNF425后,WB显示A549细胞中的JNK和P38活性受到抑制。因此,推测ZNF425可能具有抑制早中期肺癌的功能,而且这种能力与MAPK信号通路具有相关性。

In order to study the relationship between ZNF425 and lung cancer,this paper first applied bioinformatics methods to study the correlation between ZNF425 and lung cancer.Based on the Cancer Genome Atlas(TCGA)database and the Common Database for Cancer and Normal Gene Expression Profile Analysis(GEPIA),the expression of ZNF425 in two lung cancer subtypes LUAD(lung adenocarcinoma)and LUSC(pulmonary squamous cell carcinoma)data was analyzed by post-operations.We found that ZNF425 expression was reduced in cancer tissues.This phenomenon is particularly significant in Stage III lung cancer.Our results also show that patients with a high level of ZNF425 expression had higher survival rates.We then utilized the human lung cancer sample IHC to confirm the bioinformatics analysis results.In comparison with the adjacent tissues,ZNF425 inⅠ,Ⅱ,andⅢcancer tissues was found to be significantly down-regulated.Finally,ZNF425 overexpression plasmid was constructed in this work.After transient overexpression of ZNF425 in lung cancer A549 cell lines,the inhibition of JNK and P38 activities was observed.Based on these results,we speculate that ZNF425 may have the ability to suppress early and middle stage lung cancer,and this ability has to do with the MAPK signaling pathway.