EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL

作者全名："Pan, Mingang; Luo, Muyu; Liu, Lele; Chen, Yunmeng; Cheng, Ziyi; Wang, Kai; Huang, Luyi; Tang, Ni; Qiu, Jianguo; Huang, Ailong; Xia, Jie"

作者地址："[Pan, Mingang; Luo, Muyu; Liu, Lele; Chen, Yunmeng; Cheng, Ziyi; Wang, Kai; Huang, Luyi; Tang, Ni; Huang, Ailong; Xia, Jie] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China; [Qiu, Jianguo] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China"

通信作者："Huang, AL; Xia, J (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China.; Qiu, JG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China."

来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001151695100001

JCR分区：Q1

影响因子：11.3

年份：2024

卷号：43

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：HCC; EGR1; PFKL; Glycolysis; Sorafenib

摘要："BackgroundHepatocellular Carcinoma (HCC) is a matter of great global public health importance; however, its current therapeutic effectiveness is deemed inadequate, and the range of therapeutic targets is limited. The aim of this study was to identify early growth response 1 (EGR1) as a transcription factor target in HCC and to explore its role and assess the potential of gene therapy utilizing EGR1 for the management of HCC.MethodsIn this study, both in vitro and in vivo assays were employed to examine the impact of EGR1 on the growth of HCC. The mouse HCC model and human organoid assay were utilized to assess the potential of EGR1 as a gene therapy for HCC. Additionally, the molecular mechanism underlying the regulation of gene expression and the suppression of HCC growth by EGR1 was investigated.ResultsThe results of our investigation revealed a notable decrease in the expression of EGR1 in HCC. The decrease in EGR1 expression promoted the multiplication of HCC cells and the growth of xenografted tumors. On the other hand, the excessive expression of EGR1 hindered the proliferation of HCC cells and repressed the development of xenografted tumors. Furthermore, the efficacy of EGR1 gene therapy was validated using in vivo mouse HCC models and in vitro human hepatoma organoid models, thereby providing additional substantiation for the anti-cancer role of EGR1 in HCC. The mechanistic analysis demonstrated that EGR1 interacted with the promoter region of phosphofructokinase-1, liver type (PFKL), leading to the repression of PFKL gene expression and consequent inhibition of PFKL-mediated aerobic glycolysis. Moreover, the sensitivity of HCC cells and xenografted tumors to sorafenib was found to be increased by EGR1.ConclusionOur findings suggest that EGR1 possesses therapeutic potential as a tumor suppressor gene in HCC, and that EGR1 gene therapy may offer benefits for HCC patients."

基金机构：Jie xia

基金资助正文："We sincerely thank Prof. Yuan Hu and Ni Tang (Key Laboratory of Molecular Biology on Infectious Diseases, Chongqing Medical University) for supplying the plasmids used in this research."