1. Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a.
- Author
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Wu, Hua-Qing, Cheng, Mei-Ling, Lai, Jin-Mei, Wu, Hsuan-Hui, Chen, Meng-Chun, Liu, Wen-Huan, Wu, Wu-Hsiung, Chang, Peter Mu-Hsin, Huang, Chi-Ying F., Tsou, Ann-Ping, Shiao, Ming-Shi, and Wang, Feng-Sheng
- Subjects
WARBURG Effect (Oncology) ,HEPATOCYTE growth factor ,LIVER analysis ,EUKARYOTES ,MICRORNA ,FERROMAGNETIC materials ,MAGNETIC domain - Abstract
The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a
–/– ) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a–/– mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states. By definition of the similarity ratio, we compared the flux fold change of the genome-scale metabolic model computational results and metabolomic profiling data measured through a liquid-chromatography with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in normal and deficient states. The Ddc gene demonstrated the highest similarity ratio of 95% to the biological hypothesis of the Warburg effect, and similarity of 75% to the experimental observation. We also used 2, 6, and 11 months of mir-122 knockout mice liver cell to examined the expression pattern of DDC in the knockout mice livers to show upregulated profiles of DDC from the data. Furthermore, through a bioinformatics (LINCS program) prediction, BTK inhibitors and withaferin A could downregulate DDC expression, suggesting that such drugs could potentially alter the early events of metabolomics of liver cancer cells. [ABSTRACT FROM AUTHOR]- Published
- 2017
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