Liu Gang, Hou Guojun, Li Liang, Li Yixue, Zhou Weiping, Liu Lei
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Oncotarget. 2016 May 31;7(22):32607-16. doi: 10.18632/oncotarget.8927.
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.
关键代谢酶调节小分子化合物的通量，为细胞结构和能量提供基础底物。据报道，其中一些酶是重要的致癌和转移相关基因。在我们的研究中，我们对50对肝细胞癌（HCC）正常肿瘤样本进行了RNA测序，发现二甲基甘氨酸脱氢酶（DMGDH）在HCC中的表达降低。蛋白质印迹和免疫组织化学对蛋白质水平的分析也证实了我们的发现。在三个独立数据集中，它被证明是一种有价值的诊断和预后生物标志物。此外，我们发现DMGDH在体外和体内均能抑制迁移、侵袭和转移。通过对DMGDH进行基因表达微阵列分析，我们在过表达DMGDH的细胞系中鉴定了几种可能发生改变的途径。在这些途径中，我们注意到当DMGDH过表达时，Akt-308/473的磷酸化被显著抑制。总之，我们的研究表明，DMGDH是一种潜在的有价值的HCC诊断和预后生物标志物，并且DMGDH基因表达通过Akt信号通路抑制转移。
