Dataset Information

TET1 exerts its anti-tumor functions via demethylating DACT2 and SFRP2 to antagonize Wnt/?-catenin signaling pathway in nasopharyngeal carcinoma cells.

ABSTRACT:

Background

TET1 is a tumor suppressor gene (TSG) that codes for ten-eleven translocation methyl cytosine dioxygenase1 (TET1) catalyzing the conversion of 5-methylcytosine to 5-hydroxy methyl cytosine as a first step of TSG demethylation. Its hypermethylation has been associated with cancer pathogenesis. However, whether TET1 plays any role in nasopharyngeal carcinoma (NPC) remains unclear. This study investigated the expression and methylation of TET1 in NPC and confirmed its role and mechanism as a TSG.

Results

TET1 expression was downregulated in NPC tissues compared with nasal septum deviation tissues. Demethylation of TET1 in HONE1 and HNE1 cells restored its expression with downregulated methylation, implying that TET1 was silenced by promoter hypermethylation. Ectopic expression of TET1 suppressed the growth of NPC cells, induced apoptosis, arrested cell division in G0/G1 phase, and inhibited cell migration and invasion, confirming TET1 TSG activity. TET1 decreased the expression of nuclear ?-catenin and downstream target genes. Furthermore, TET1 could cause Wnt antagonists (DACT2, SFRP2) promoter demethylation and restore its expression in NPC cells.

Conclusions

Collectively, we conclude that TET1 exerts its anti-tumor functions in NPC cells by suppressing Wnt/?-catenin signaling via demethylation of Wnt antagonists (DACT2 and SFRP2).

SUBMITTER: Fan J

PROVIDER: S-EPMC6091063 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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TET1 exerts its anti-tumor functions via demethylating DACT2 and SFRP2 to antagonize Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma cells.

Fan Jiangxia J Zhang Yan Y Mu Junhao J He Xiaoqian X Shao Bianfei B Zhou Dishu D Peng Weiyan W Tang Jun J Jiang Yu Y Ren Guosheng G Xiang Tingxiu T

Clinical epigenetics 20180803 1

<h4>Background</h4>TET1 is a tumor suppressor gene (TSG) that codes for ten-eleven translocation methyl cytosine dioxygenase1 (TET1) catalyzing the conversion of 5-methylcytosine to 5-hydroxy methyl cytosine as a first step of TSG demethylation. Its hypermethylation has been associated with cancer pathogenesis. However, whether TET1 plays any role in nasopharyngeal carcinoma (NPC) remains unclear. This study investigated the expression and methylation of TET1 in NPC and confirmed its role and me ...[more]

PMID: 30075814

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