title: Hypermethylation of FOXD3 suppresses cell proliferation, invasion and metastasis in hepatocellular carcinoma.
abstract: As a transcriptional repressor, forkhead box D3 (FOXD3) plays an important role in tumorigenesis and progression of several tumors. However, the function and methylation status of FOXD3 remain unknown in the progression of hepatocellular carcinoma (HCC). In this study, we found that FOXD3 was decreased in HCC tissues and correlated with differentiation, AFP and poor survival of HCC patients (p<0.05). Down-regulation of FOXD3 in HCC tissues was mainly due to promoter hypermethylation. In vitro and in vivo functional results showed that ectopic FOXD3 inhibited the proliferation, migration, epithelial-mesenchymal transition (EMT) and invasion in HepG2 and SMMC-7721 cells, and FOXD3 depletion in HepG2 and QGY-7701 cells showed the adverse effects (p<0.05). Moreover, FOXD3 was sufficient to suppress tumor growth and pulmonary metastatic potential in mice. Our findings suggest that down-regulation of FOXD3, due to promoter hypermethylation plays an important role in the progression of HCC and may be a promising prognostic biomarker for HCC patients.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China; Department of Pathology, Xinxiang Medical University, Xinxiang City, 453003 Henan Province, People's Republic of china.
authors.forename: Guoyang
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China.
authors.forename: Shuiwang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Pingxiang
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Xin
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Guifeng
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515 Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515 Guangdong Province, People's Republic of China. Electronic address: redsnow007@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C503514:FOXD3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
keywords: FOXD3; Hepatocellular carcinoma; Invasion; Metastasis; Methylation