Hypermethylation of FOXD3 suppresses cell proliferation, invasion and metastasis in hepatocellular carcinoma

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• 作者：Guoyang He^a ; ^b ; ^c ; ¹ ; Shuiwang Hu^d ; ¹ ; Dan Zhang^a ; ^b ; Pingxiang Wu^a ; ^b ; Xiaohui Zhu^a ; ^b ; Sainan Xin^a ; ^b ; Guifeng Lu^a ; ^b ; Yanqing Ding^a ; ^b ; Li Liang^a ; ^b ; ^{redsnow007@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：FOXD3 ; Methylation ; Invasion ; Metastasis ; Hepatocellular carcinoma
• 刊名：Experimental and Molecular Pathology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：99
• 期：2
• 页码：374-382
• 全文大小：2408 K

文摘

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.