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).Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0535-7) contains supplementary material, which is available to authorized users.

Background and AimThe high mortality and poor prognosis of hepatocellular carcinoma (HCC) have raised the public attention. Gene therapy is considered as a promising treatment option for cancer; thus, finding a new therapeutic target for HCC is urgently needed. GATA4 is a tumor suppressor gene in multiple cancers, but its role in HCC is unclear. In this study, we explored the function of GATA4 in HCC.MethodsReverse transcription–polymerase chain reaction and quantitative polymerase chain reaction were used to detect the mRNA expression of GATA4 in HCC cells and tissues. Cell viability, transwell, colony formation, and flow cytometry assays were applied to examine different aspects of biological effects of GATA4 in vitro. Xenografts, immunohistochemistry, and terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling assays were performed to evaluate the effect of GATA4 on tumorigenicity in vivo. Western blotting, immunofluorescence, and β‐galactosidase staining were used to investigate the mechanism underlying the function of GATA4.ResultsWe found that GATA4 was silenced in 15/19 (79%) HCC tissues. Restoring the expression of GATA4 induced G0/G1 phase arrest, promoted apoptosis, suppressed HCC proliferation in vitro, and inhibited HCC tumor growth in vivo. Our data further showed that the ectopic expression of GATA4 induced cellular senescence through regulating nuclear factor‐κB and inducing mesenchymal‐to‐epithelial transition.ConclusionsOur data demonstrated that by inducing cellular senescence and mesenchymal‐to‐epithelial transition, GATA4 plays a crucial role as a tumor suppressor in HCC. It may thus be a potential cancer therapeutic target for HCC.

In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1‐promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro. We also observed that PLCD1 suppressed proliferation and promoted apoptosis in vivo. In addition, PLCD1 induced G1/S phase cell cycle arrest. Furthermore, we found that PLCD1 led to the downregulation of several factors downstream of β‐catenin, including c‐Myc and cyclin D1, which are generally known to be promoters of tumorigenesis. This downregulation was caused by an upregulation of E‐cadherin in colorectal tumor cells. Our findings provide insights into the role of PLCD1 as a tumor suppressor gene in colorectal cancer (CRC), and demonstrate that it plays significant roles in proliferation, migration, invasion, cell cycle progression, and epithelial‐mesenchymal transition. On the basis of these results, tumor‐specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in CRC.

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