转录因子SP1调控肝细胞癌中三元基序家族蛋白7基因表达的机制

被引：2

作者：

樊昌宇

丁涵

徐乙冉

咸蕊

闫凤娟

机构：

[1] 江苏师范大学生命科学学院生物化学与分子生物学教研室

来源：

中国生物化学与分子生物学报 | 2023年 / 39卷 / 09期

关键词：

肝细胞癌; 转录调控; 启动子; 三元基序家族蛋白7; 特异性蛋白1;

D O I：

10.13865/j.cnki.cjbmb.2023.06.1072

中图分类号：

R735.7 [肝肿瘤];

学科分类号：

100214 ;

摘要：

三元基序家族蛋白7 (tripartite motif-containing protein 7, TRIM7)作为E3泛素连接酶TRIM家族的成员，在免疫调控、代谢等生理过程中发挥重要调控作用。此外，TRIM7的异常表达与肝细胞癌(hepatocellular carcinoma, HCC)的发生发展密切相关并呈现出复杂的调控作用，但其在HCC中的表达调控机制尚不清楚。本研究首先利用多种在线数据库分析发现，TRIM7在HCC中高表达，并且TRIM7高表达的肝细胞癌患者预后较差；利用UCSC、JASPAR数据库分析预测TRIM7基因启动子区的转录因子结合位点。结果显示，TRIM7启动子上含有4个特异性蛋白1(specificity protein 1,SP1)转录因子结合位点。本研究利用双荧光素酶报告实验、ChIP-PCR方法检测发现，SP1通过直接结合在TRIM7启动子上的SP1结合位点，从而正调控TRIM7启动子驱动的转录活性。RT-qPCR、Western印迹检测结果进一步显示，过表达SP1在mRNA和蛋白质水平均上调TRIM7基因的表达(P<0.01),且利用SP1抑制剂Mithramycin A处理能够逆转SP1对TRIM7基因表达的调控作用(P<0.01)。总之，本研究初步揭示了TRIM7在肝细胞癌中高表达的调控机制，为深入研究该基因功能以及早期诊断、靶向治疗提供重要的理论依据。

引用

页码：1314 / 1321

页数：8

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