Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells
机构:[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan,People’s Republic of China[2]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China[3]Academician (Expert)Workstation of Sichuan Province, Luzhou,Sichuan, People’s Republic of China[4]The Department of Urology, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of South University of Science and Technology of China, Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen, Guangdong,People’s Republic of China深圳市康宁医院深圳市人民医院深圳医学信息中心[5]Shenzhen Public Service Platform on Tumor Precision Medicineand Molecular Diagnosis, Shenzhen, Guangdong,People’s Republic of China[6]South Sichuan Institute of Translational Medicine, Luzhou,Sichuan, People’s Republic of China
Objective: The Warburg effect, also known as aerobic glycolysis, plays a dominant role in the development of gastrointestinal (GI) cancers. In this study, we analyzed the expression of key genes involved in the Warburg effect in GI cancers and investigated the effect of suppressing the Warburg effect in vitro in liver cancer cell lines. Methods: The Cancer Genome Atlas (TCGA) RNA-Seq data were used to determine gene expression levels, which were analyzed with GraphPad Prism 7.00. Genetic alterations were queried with cBioPortal. The influence of the Warburg effect on liver cancer cell viability, migration and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined by means of MTT, transwell and GAPDH activity assays. Results: The levels of expression of genes associated with the Warburg effect were increased in tumors. To our knowledge, this is the first report of upregulated expression of CUEDC2, HMGB2, PFKFB4, PFKP and SIX1 in liver cancer. Clinically, overexpression of these genes was associated with significantly worse overall survival of liver cancer patients. In vitro, selective inhibition of GADPH suppressed the growth and metastasis of Huh-7, Bel7404 and Hep3B hepatocellular carcinoma cell lines. Conclusion: The Warburg effect may play an important role in GI cancers, especially in liver cancer.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81503093, 81602166, 81672444]; Southwest Medical University [2016LZXNYD-T01, 2017LZXNYD-Z05, 2017LZXNYD-J09]
第一作者机构:[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan,People’s Republic of China[3]Academician (Expert)Workstation of Sichuan Province, Luzhou,Sichuan, People’s Republic of China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan,People’s Republic of China[2]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China[3]Academician (Expert)Workstation of Sichuan Province, Luzhou,Sichuan, People’s Republic of China[6]South Sichuan Institute of Translational Medicine, Luzhou,Sichuan, People’s Republic of China[*1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of China[*2]Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China
推荐引用方式(GB/T 7714):
Xinyue Zhang,Jinan Guo,Parham Jabbarzadeh Kaboli,et al.Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells[J].ONCOTARGETS AND THERAPY.2020,13:7295-7304.doi:10.2147/OTT.S257944.
APA:
Xinyue Zhang,Jinan Guo,Parham Jabbarzadeh Kaboli,Qijie Zhao,Shixin Xiang...&QinglianWen.(2020).Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells.ONCOTARGETS AND THERAPY,13,
MLA:
Xinyue Zhang,et al."Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells".ONCOTARGETS AND THERAPY 13.(2020):7295-7304