Abstract
BackgroundTET1 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.ResultsTET1 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 β-catenin and downstream target genes. Furthermore, TET1 could cause Wnt antagonists (DACT2, SFRP2) promoter demethylation and restore its expression in NPC cells.ConclusionsCollectively, we conclude that TET1 exerts its anti-tumor functions in NPC cells by suppressing Wnt/β-catenin signaling via demethylation of Wnt antagonists (DACT2 and SFRP2).
Highlights
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 tumor suppressor genes (TSGs) demethylation
TET1 expression is downregulated in nasopharyngeal carcinoma (NPC) cell lines Our previous studies found that TET1, 2, and 3 are expressed in human adult and fetal tissues and that only TET1 was downregulated in NPC cell lines [29]
Hematoxylin and eosin (H&E) staining showed normal epithelial and cancer cell morphology and IHC staining showed that both TET1 and 5-hydroxymethyl cytosine (5hmC) expression were higher in 3 normal septum deviation than in 33 NPC tissues (Fig. 1a, b)
Summary
TET1 is a tumor suppressor gene (TSG) that codes for ten-eleven translocation methyl cytosine dioxygenase (TET1) catalyzing the conversion of 5-methylcytosine to 5-hydroxy methyl cytosine as a first step of TSG demethylation. In NPC, many tumor suppressor genes (TSGs), such as PCDH20 [7], WIF1 [7, 8], RASSF1 [9], ADAMTS18 [10], PTPRG [11], CDH4 [12], CDH11 [13], SOX11 [14], and DACT2 [15], The ten-eleven translocation (TET) proteins, TET1, TET2, and TET3 are highly active DNA cytosine oxygenases that maintain TSGs in an unmethylated state by conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) or by competition with DNA methyltransferases resulting in passive demethylation [17, 18].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
