Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.
Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.
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FAM83D上调影响肝细胞癌的增殖和侵袭
DOI：
10.18632/oncotarget.4432
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发表时间：
2015-09-15
期刊：
影响因子：
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通讯作者：
Huang J
中科院分区：
文献类型：
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作者：
Liao W;Liu W;Liu X;Yuan Q;Ou Y;Qi Y;Huang W;Wang Y;Huang J
潜在癌基因的发现在寻找许多癌症的新治疗靶点方面发挥着重要作用，其中肝细胞癌是世界上最常见的癌症之一。在我们之前的研究中，利用基因芯片技术，我们发现FAM83D在肝癌中过表达。然而，FAM83D的过度表达是否与肝癌的发生有关尚不清楚。在本研究中，我们发现与癌旁肝组织相比，76.6%(167/218)的肝细胞癌组织中FAM83D在mRNA水平上表达上调，69.44%(50/72)的肝细胞癌组织中FAM83D基因在蛋白水平上表达上调。FAM83DmRNA表达水平与甲胎蛋白水平(AFP)(100 ng/ml)、临床分期、门静脉癌栓、无瘤生存期(DFS)和总生存期(OS)呈正相关(P<；0.05)。RNA干扰实验表明，FAM83D基因的敲除显著促进了Huh7和HepG2细胞的生长。此外，在FAM83D基因过表达的肝细胞癌标本中，FAM83D启动子的DNA甲基化状态显著降低。我们的数据表明，潜在的癌目标基因FAM83D的上调可能是由表观遗传事件触发的，可能有助于肝癌的发生。
The identification of potential oncogenes plays an important role in finding novel therapeutic targets for many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. In our previous research, using microarray technology, we found that FAM83D was overexpressed in HCCs. However, whether the overexpression of FAM83D contributes to hepatocarcinogenesis remains unclear. In this study, we found that FAM83D was significantly upregulated in 76.6% (167 of 218) of the HCC specimens at the mRNA level and in 69.44% (50 of 72) of the HCC specimens at the protein level compared with adjacent non-cancerous liver specimens, as indicated by RT-PCR and immunohistochemical staining, respectively. The FAM83DmRNA expression level was positively correlated with the level of alpha-fetoprotein (AFP) (≥100 ng/ml), the clinical TNM stage, the presence of a portal vein tumor thrombus (PVTT), disease-free survival (DFS) and the overall survival (OS) time of the HCC patients (P < 0.05). Knocking down FAM83D significantly promoted the growth of Huh7 and HepG2 cells, as demonstrated in an RNA interference assay. Moreover, the DNA methylation status of the FAM83D promoter was significantly reduced in the HCC specimens with overexpression of FAM83D gene. Our data suggest that the upregulation of FAM83D, a potential oncotarget gene, may be triggered by epigenetic events and can contribute to hepatocarcinogenesis.