Analysis of Key Genes Regulating the Warburg Effect in Patients with Gastrointestinal Cancers and Selective Inhibition of This Metabolic Pathway in Liver Cancer Cells

胃肠道癌症患者Warburg效应关键基因调控分析及肝癌细胞中该代谢途径的选择性抑制

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作者:Xinyue Zhang #, Jinan Guo #, Parham Jabbarzadeh Kaboli, Qijie Zhao, Shixin Xiang, Jing Shen, Yueshui Zhao, Fukuan Du, Xu Wu, Mingxing Li, Huijiao Ji, Xiao Yang, Zhangang Xiao, Qinglian Wen

Conclusion

The Warburg effect may play an important role in GI cancers, especially in liver cancer.

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.

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.

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.

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