Key enzymes are important biomarkers for carcinogenesis, metastasis and further for therapy. In recent work by Prof. LI Yixue’s lab at Institute of Biochemistry and Cell Biology (SIBCB), Institutions of Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences(CAS) and co-workers, they discovered that dimethylglycine dehydrogenase (DMGDH), an enzyme involved in degrading choline to glycine is down-regulated in both hepatocellular carcinoma (HCC) genesis and metastasis by over 65% according to the expression of 50 pair of normal-tumor tissues evaluated by RNA-seq. The mRNA and protein level in tumor and normal are significantly different, and mRNA can be used as a potentail biomarker in distinguishing normal and tumors.
Further analysis reveals that important clinical information including survival, is also correlated with DMGDH expression level. Over expression and knock down of DMGDH promotes the migration, invasion and wound healing ability of HCC cell lines both in vivo and in vitro.
To further evaluate how DMGDH impact on the migration of HCC cells, the transcriptome of DMGDH/GFP over-expression cells was measured by microarray. Several cancer metastasis related pathways were identified. Among them, Akt is a well known pathway for metastasis, further experiments validated that the phosphorylation level of Akt 308/473 were lower in presence of DMGDH.
After over expression of DMGDH, a lot of genes involved in cancerous pathwys was significantly altered, it suggested that the impact of metabolomics on cancer transcriptome is more huge than we thought.
This study entitled “Potential Dianostic and Prognostic Marker DMGDH Suppresses Hepatocellular Carcinoma Metastasis In vitro and In vivo” was published online by Oncotarget on 22 April, 2016.
This work was supported by grants from National High-tech R&D Program (863 Program) and National Science and Technology Major Project of China.
CONTACT:
LI Yixue, Institutions of Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200031, China.
Email: yxli@picb.ac.cn
DMGDH has a good performace as a biomarker for both diagnosis and prognosis. Migration and invasion rate of cells in presence of DMGDH is significantly lower; according to gene expression microarray, several pathways were altered. Molecular experiments validated that phophorylation of Akt308/473 were lower in presence of DMGDH (Image provided by Prof. LI Yixue’s lab)
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