Reduced expression of DACT2 promotes hepatocellular carcinoma progression: involvement of methylation-mediated gene silencing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-03-07

AUTHORS

Sheng Gao, Zhe Yang, Zhi-Yun Zheng, Jia Yao, Feng Zhang, Li-Ming Wu, Hai-Yang Xie, Lin zhou, Shu-Sen Zheng

ABSTRACT

BackgroundHepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of HCC; however, the molecular mechanisms that lead to hepatocarcinogenesis and progression are still not clearly understood.MethodsThe expression of DACT2 in specimens from 30 paired HCCs and an additional 61 HCC patients after liver transplantation was evaluated by quantitative RT-PCR and immunohistochemical analysis. We investigated the methylation status of the DACT2 promoter region. We also analyzed the alterations of the cell cycle, migration and invasion after DACT2 knockdown.ResultsThe expression level of DACT2 was significantly lower in HCC tissues than in non-cancerous tissues. Reduced DACT2 expression was associated with large tumor size. DACT2 transcripts were at low levels in hypermethylated liver cancer cells and were restored by exposure to a demethylating agent. Reduced expression of DACT2 in MHCC97L cells induced G1/S arrest, increased cell proliferation, and promoted cell invasion.ConclusionsOur study suggests that DACT2 is silenced by promoter hypermethylation, and reduced DACT2 can promote liver cancer progression. DACT2 may serve as a novel tumor suppressor gene in HCC. More... »

PAGES

57

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1477-7819-11-57

DOI

http://dx.doi.org/10.1186/1477-7819-11-57

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https://app.dimensions.ai/details/publication/pub.1052880887

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23496880


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58 arrest
59 cancer cells
60 cancer progression
61 carcinoma
62 carcinoma progression
63 cell cycle
64 cell invasion
65 cell proliferation
66 cells
67 cycle
68 demethylating agent
69 exposure
70 expression
71 expression levels
72 genes
73 hepatocarcinogenesis
74 hepatocellular carcinoma progression
75 humans
76 hypermethylation
77 immunohistochemical analysis
78 invasion
79 involvement
80 knockdown
81 larger tumor size
82 levels
83 liver cancer cells
84 liver cancer progression
85 liver transplantation
86 low levels
87 malignancy
88 mechanism
89 methylation status
90 methylation-mediated gene
91 migration
92 molecular mechanisms
93 non-cancerous tissues
94 novel tumor suppressor gene
95 pathogenesis
96 pathogenesis of HCC
97 patients
98 prognosis
99 progression
100 proliferation
101 promoter hypermethylation
102 promoter region
103 quantitative RT-PCR
104 reduced expression
105 region
106 size
107 specimens
108 status
109 study
110 suppressor gene
111 surgery
112 tissue
113 transcripts
114 transplantation
115 tumor size
116 tumor suppressor gene
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