前列腺癌中PI3K/AKT通路调控PHF19基因表达的机制研究
Mechanism research of PI3K/AKT pathway regulating PHF19 gene expression in prostate cancer
明道靖 1郭梦梦 1张晋辉 2刘梦洋 3史明慧 3刘姝言 3袁帅 2曾宪涛4
作者信息
- 1. 河南大学淮河医院泌尿外科(河南开封 475000);武汉大学中南医院循证与转化医学中心(武汉 430071)
- 2. 武汉大学中南医院循证与转化医学中心(武汉 430071)
- 3. 武汉大学中南医院循证与转化医学中心(武汉 430071);武汉大学中南医院泌尿外科(武汉 430071)
- 4. 河南大学淮河医院泌尿外科(河南开封 475000);武汉大学中南医院循证与转化医学中心(武汉 430071);武汉大学中南医院泌尿外科(武汉 430071)
- 折叠
摘要
目的 探讨前列腺癌中PI3K/AKT通路对PHF19 基因表达的调控作用.方法 利用LY294002 和EGF处理PC-3 细胞,随后采用qRT-PCR检测TP63、ΔNp63、PHF19 mRNA的表达;利用ChIPBase、JASPAR数据库预测调控PHF19 基因的转录因子;利用GEPIA 2 数据库分析TP53、TP63 与PHF19 基因mRNA的表达相关性;利用ChIP-qPCR检测ΔNp63蛋白结合PHF19基因启动子的情况.结果 PI3K/AKT通路抑制剂LY294002 可显著抑制PHF19 基因mRNA表达(不同时间处理组相比P＜0.05);PI3K/AKT通路激动剂EGF可显著促进PHF19 mRNA表达(不同时间处理组相比P＜0.05).在前列腺癌组织中TP63 mRNA与PHF19 mRNA表达正相关(r=0.43,P＜0.05).ΔNp63 蛋白可结合PHF19 基因的启动子区域(P＜0.05).LY294002 还可显著抑制TP63、ΔNp63 mRNA的表达(不同时间处理组相比P＜0.05).结论 PI3K/AKT通路可通过转录因子TP63 促进PHF19基因的表达.
Abstract
Objective To investigate the regulatory effect of the PI3K/AKT pathway on PHF19 gene expression in prostate cancer.Methods PC-3 cells were treated with the PI3K/AKT pathway inhibitor LY294002 or the activator EGF.Subsequently,the expression of TP63,ΔNp63 and PHF19 mRNA was detected using quantitative reverse transcription PCR(qRT-PCR).Potential transcription factors involved in PHF19 gene regulation were predicted using ChIPBase and JASPAR databases.The correlation between mRNA expressions of TP53,TP63 and PHF19 genes was analyzed through the GEPIA 2 database.Chromatin immunoprecipitation followed by quantitative PCR(ChIP-qPCR)was employed to assess the binding of ΔNP63 protein to the PHF19 gene promoter.Results LY294002 significantly reduced PHF19 mRNA expression(compared with different time treatment groups,P＜0.05),while EGF notably enhanced the PHF19 mRNA expression(compared with different time treatment groups,P＜0.05).TP63 mRNA was positively correlated with PHF19 mRNA expression in prostate cancer tissues(r=0.43,P＜0.05).ΔNp63 could bind to the promoter region of the PHF19 gene.LY294002 also significantly reduced the expression of both TP63 and ΔNp63 mRNA(compared with different time treatment groups,P＜0.05).Conclusion The PI3K/AKT pathway may enhance PHF19 gene expression via the transcription factor TP63.
关键词
PI3K/AKT/TP63/PHF19/前列腺癌Key words
PI3K/AKT/TP63/PHF19/Prostate cancer引用本文复制引用
基金项目
国家自然科学基金面上项目(82373411)
湖北省自然科学基金面上项目(2023AFB742)
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据