title: 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.
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Liao
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.|Key Laboratory of Systems Biomedicine (Ministry of Education), Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.|Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.|Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D019175:DNA Methylation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011169:Portal Vein / Q000473:pathology; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology; D016896:Treatment Outcome; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C530359:FAM83D protein, human; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D000509:alpha-Fetoproteins
keywords: FAM83D; hepatocellular carcinoma; methylation; overall survival; up-regulation