Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis <i>in vitro</i> and <i>in vivo</i>

Abstract

// Gang Liu 1, * , Guojun Hou 2, * , Liang Li 3, * , Yixue Li 1, # , Weiping Zhou 2 , Lei Liu 4 1 Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 2 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, National Center for Liver Cancer, Shanghai, China 4 Institute of Biomedical Sciences, Fudan University, Shanghai, China * These authors contributed equally to this work # Co-authors Correspondence to: Lei Liu, email: liulei@fudan.edu.cn Weiping Zhou, email: ehphwp3@126.com Keywords: hepatocellular carcinoma, diagnosis, prognosis, metastasis, DMGDH Received: January 28, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: March 31, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: April 22, 2016 ABSTRACT Key metabolic enzymes regulatethe fluxes of small compounds to provide the basal substrates for cellular architecture and energy. Some of them are reported to be important carcinogenesis- and metastasis-related genes. In our work, we performed RNA-seq for50 pairs of normal-tumor of hepatocellular carcinoma (HCC) samples and found that the expression of dimethylglycine dehydrogenase (DMGDH) is decreased in HCC. The analysis of protein levels with Western blotting and immunohistochemistry also conformed our findings. It is proven to be a valuable biomarker for both diagnosis and prognosis in three independent datasets. Furthermore, we revealed that DMGDH suppresses migration, invasion and metastasis both in vitro and in vivo . By utilizing gene expression microarray for DMGDH, we identified several possible pathways altered in a DMGDH over-expressing cell line. Among these pathways, we noted that the phosphorylation of Akt-308/473 was significantly suppressed when DMGDH was over-expressed. In summary, our work reveals that DMGDH is a potential valuable biomarker for both diagnosis and prognosisfor HCC, and DMGDH gene expression suppresses metastasis through the Akt signaling pathway.