Dataset Information

Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.

ABSTRACT: 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.

SUBMITTER: Liao W

PROVIDER: S-EPMC4695175 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.

Liao Weijia W Liu Weilong W Liu Xing X Yuan Qing Q Ou Ying Y Qi Yao Y Huang Wanqiu W Wang Yun Y Huang Jian J

Oncotarget 20150901 27

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 2 ...[more]

PMID: 26125229

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Project description:BackgroundPeripheral serotonin is involved in tumorigenesis and induces a pro-proliferative effect in hepatocellular carcinoma (HCC) cells; however, the intracellular mechanisms by which serotonin exerts a mitogenic effect remain unclear. In this research, we examined whether FOXO3a, a transcription factor at the interface of crucial cellular processes, plays a role downstream of serotonin in HCC cells.ResultsThe cell viability and expression of FOXO3a was assessed in three HCC cell lines (Huh7, HepG2 and Hep3B) during serum deprivation in the presence or absence of serotonin. Serum free media significantly inhibited HCC proliferation and led to reduced expression and nuclear accumulation of FOXO3a. Knockdown of FOXO3a enhanced the ability of serum deprivation to inhibit HCC cells proliferation. And overexpression of non-phosphorylated FOXO3a in HCC cells reversed serum-deprivation-induced growth inhibition. Serotonin reversed the serum-deprivation-induced inhibition of cell proliferation and upregulated FOXO3a in Huh7 cells; however, serotonin had no effect on the proliferation of serum-deprived HepG2 or Hep3B cells. In addition to proliferation, serotonin also induced phosphorylation of AKT and FOXO3a in serum-deprived Huh7 cells but not in HepG2 and Hep3B cells. However, the phosphorylation of FOXO3a induced by serotonin did not export FOXO3a from nucleus to cytoplasm in serum-deprived Huh7 cells. Consequently, we demonstrated that serotonin promoted the proliferation of Huh7 cells by increasing the expression of FOXO3a. We also provide preliminary evidence that different expression levels of the 5-HT2B receptor (5-HT2BR) may contribute to the distinct effects of serotonin in different serum-deprived HCC cells.ConclusionsThis study demonstrates that FOXO3a functions as a growth factor in serum-deprived HCC cells and serotonin promotes the proliferation of serum-deprived HCC cells via upregulation of FOXO3a, in the presence of sufficient levels of the serotonin receptor 5-HT2BR. Drugs targeting the serotonin-5-HT2BR-FOXO3a pathway may provide a novel target for anticancer therapy.

Dataset Information

Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.

Publications

Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma.

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