Gene Summary

Gene:TET1; tet methylcytosine dioxygenase 1
Aliases: LCX, CXXC6, bA119F7.1
Summary:DNA methylation is an epigenetic mechanism that is important for controlling gene expression. The protein encoded by this gene is a demethylase that belongs to the TET (ten-eleven translocation) family. Members of the TET protein family play a role in the DNA methylation process and gene activation. [provided by RefSeq, Sep 2015]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:methylcytosine dioxygenase TET1
Source:NCBIAccessed: 31 August, 2019


What does this gene/protein do?
Show (12)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Succinic Acid
  • Messenger RNA
  • Gene Expression Profiling
  • Signal Transduction
  • Transforming Growth Factor beta
  • CpG Islands
  • Cell Proliferation
  • Colorectal Cancer
  • Chromosome 10
  • Cell Movement
  • Testis
  • Prostate Cancer
  • Epigenetics
  • Uterine Cancer
  • Neoplasm Invasiveness
  • Cytosine
  • Down-Regulation
  • Dioxygenases
  • DNA Methylation
  • Receptors, GABA-A
  • DNA-Binding Proteins
  • 5-Methylcytosine
  • Cancer Gene Expression Regulation
  • Neoplastic Cell Transformation
  • Tumor Suppressor Proteins
  • Biomarkers, Tumor
  • Acute Lymphocytic Leukaemia
  • Leukaemia
  • Transcription Factors
  • DNA (Cytosine-5-)-Methyltransferases
  • Mixed Function Oxygenases
  • Immunohistochemistry
  • TET1
  • bcl-2-Associated X Protein
  • MLL
  • DNA Sequence Analysis
  • p38 Mitogen-Activated Protein Kinases
  • Rats, Wistar
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Tandem Mass Spectrometry
  • Histones
  • Promoter Regions
  • Mutation
Tag cloud generated 31 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: TET1 (cancer-related)

Wang P, Yan Y, Yu W, Zhang H
Role of ten-eleven translocation proteins and 5-hydroxymethylcytosine in hepatocellular carcinoma.
Cell Prolif. 2019; 52(4):e12626 [PubMed] Related Publications
In mammals, methylation of the 5th position of cytosine (5mC) seems to be a major epigenetic modification of DNA. This process can be reversed (resulting in cytosine) with high efficiency by dioxygenases of the ten-eleven translocation (TET) family, which perform oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine. It has been demonstrated that these 5mC oxidation derivatives are in a dynamic state and have pivotal regulatory functions. Here, we comprehensively summarized the recent research progress in the understanding of the physiological functions of the TET proteins and their mechanisms of regulation of DNA methylation and transcription. Among the three TET genes, TET1 and TET2 expression levels have frequently been shown to be low in hepatocellular carcinoma (HCC) tissues and received most attention. The modulation of TET1 also correlates with microRNAs in a post-transcriptional regulatory process. Additionally, recent studies revealed that global genomic 5hmC levels are down-regulated in HCC tissues and cell lines. Combined with the reported results, identification of 5hmC signatures in HCC tissues and in circulating cell-free DNA will certainly contribute to early detection and should help to design therapeutic strategies against HCC. 5hmC might also be a novel prognostic biomarker of HCC. Thus, a detailed understanding of the molecular mechanisms resulting in the premalignant and aggressive transformation of TET proteins and cells with 5hmC disruption might help to develop novel epigenetic therapies for HCC.

Kondo Y
Genome-Epigenome-Senescence: Is TET1 a Caretaker of p53-Injured Lung Cancer Cells?
Cancer Res. 2019; 79(8):1751-1752 [PubMed] Related Publications
The study by Filipczak and colleagues identified the interplay between mutant p53 proteins and methylcytosine dioxygenase ten-eleven translocation 1 (TET1) in lung cancers. p53 transversion mutations were closely associated with high TET1 expression, which prevented genomic instability-associated cellular senescence. Depletion of TET1 was synergistic with classical antitumor drugs, such as cisplatin or doxorubicin, providing an attractive rationale for targeted therapies against TET1 combined with antitumor drugs in patients with p53-mutant lung cancer.

Jiang Y, Chen X, Wei Y, et al.
Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression.
Biomed Pharmacother. 2019; 113:108712 [PubMed] Related Publications
Progestins has been used widely for endometrial cancer (EC) patients. However, long term use of high dose progestin often lead to progestin resistance. Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer. Recent studies have demonstrated the role of Ten-eleven translocation 1 (TET1) in endometrial cancer, but the physiological role of TET1 in GLOI-mediated progestin resistance has been poorly addressed. Immunohistochemistry was used to detect the expression of TET1, GLOI and 5hmC in various endometrium. Western blot was carried out to analyses TET1 and GLOI expression with different treatment. Cell counting kit-8 was used to evaluate cell proliferation after various treatment. Dot blot assay and HMeDIP assay were performed to detect global hydroxmethylation levels and hydroxymethylation levels in GLOI gene respectively. In current study, we found that metformin effectively sensitized progestin in endometrial cancer cell lines through the down regulation of the expression of TET1 and GLOI. Interestingly, the exogenous increase of TET1 expression enhanced total 5hmC level and hydroxymethylation modification in glyoxalase I promoter region. This effect was abated by metformin treatment. Moreover, the expression profile of TET1 and glyoxalase I in various endometrial tissue parallelized with 5hmC level. Therefore, this finding suggests that metformin sensitized progestin in endometrial cancer through the TET1-5hmC-GLOI signaling pathway.

Li M, Tang Y, Li Q, et al.
Mono-ADP-ribosylation of H3R117 traps 5mC hydroxylase TET1 to impair demethylation of tumor suppressor gene TFPI2.
Oncogene. 2019; 38(18):3488-3503 [PubMed] Related Publications
Recently, nuclear poly-ADP-ribosylation had aroused research interest in epigenetics, but little attempt to explore functions of mono-ADP-ribosylation of histone, the major formation of histone ADP-ribosylated modification. We have previously reported a novel mono-ADP-ribosylation of H3R117, which promoted proliferation of LoVo cells. Here we showed that mono-ADP-ribosylated H3R117 of LoVo cells depressed demethylation of tumor suppressor TFPI2 promoter by suppressing TET1 expression and adjusting H3K9me3 enrichment of TFPI2 promoter to attenuate affinity of TET1, besides, since high H3K27me3 level was associated with hypermethylation, mono-ADP-ribosylated-H3R117-depended-H3K27me3 of TFPI2 promoter may contribute to hypermethylation of TFPI2. However, H3R117A mutation increased poly-ADP-ribosylated modification of TET1 promoter not TFPI2 promoter, which resulted in boosting transcription and expression of TET1 by altering DNA methylated modification, chromatin accessibility, and histone-methylated modification of TET1 promoter, while knockout TET1 of H3R117A LoVo cells directly led to hypermethylation of TFPI2 promoter and depression of TFPI2 secretion as well as enhanced proliferation, suggested that TET1 played a key role in demethylation of TFPI2, production of TFPI2, and cell proliferation. Bioinformatics analyses reveal prevalent hypermethylation of TFPI2 was an early event in tumorigenesis of colorectal caner, and expression of TET1 and TFPI2 was positive correlation in colorectal cancer and normal tissue. These data suggested that mono-ADP-ribosylation of H3R117 upregulated methylation of TFPI2 by impact TET1, since hypermethyaltion of TFPI2 was an early event in tumorigenesis, selectively target mono-ADP-ribosylation of H3R117 deficiency could be a feasible way to block tumorigenesis of colorectal cancer.

Zhu J, Huang G, Hua X, et al.
CD44s is a crucial ATG7 downstream regulator for stem-like property, invasion, and lung metastasis of human bladder cancer (BC) cells.
Oncogene. 2019; 38(17):3301-3315 [PubMed] Related Publications
Over half a million US residents are suffering with bladder cancer (BC), which costs a total $4 billion in treatment annually. Although recent studies report that autophagy-related gene 7 (ATG7) is overexpressed in BCs, the regulatory effects of ATG7 on cancer stem-like phenotypes and invasion have not been explored yet. Current studies demonstrated that the deficiency of ATG7 by its shRNA dramatically reduced sphere formation and invasion in vitro, as well as lung metastasis in vivo in human invasive BC cells. Further studies indicated that the knockdown of ATG7 attenuated the expression of CD44 standard (CD44s), while ectopic introduction of CD44s, was capable of completely restoring sphere formation, invasion, and lung metastasis in T24T(shATG7) cells. Mechanistic studies revealed that ATG7 overexpression stabilized CD44s proteins accompanied with upregulating USP28 proteins. Upregulated USP28 was able to bind to CD44s and remove the ubiquitin group from CD44s' protein, resulting in the stabilization of CD44s protein. Moreover, ATG7 inhibition stabilized AUF1 protein and thereby reduced tet1 mRNA stability and expression, which was able to demethylate usp28 promoter, reduced USP28 expression, finally promoting CD44s degradation. In addition, CD44s was defined to inhibit degradation of RhoGDIβ, which in turn promotes BC invasion. Our results demonstrate that CD44s is a key ATG7 downstream regulator of the sphere formation, invasion, and lung metastasis of BCs, providing significant insight into understanding the BC invasions, metastasis, and stem-like properties.

Filipczak PT, Leng S, Tellez CS, et al.
p53-Suppressed Oncogene TET1 Prevents Cellular Aging in Lung Cancer.
Cancer Res. 2019; 79(8):1758-1768 [PubMed] Article available free on PMC after 15/04/2020 Related Publications
The role of transcriptional regulator ten-eleven translocation methylcytosine dioxygenease 1 (TET1) has not been well characterized in lung cancer. Here we show that TET1 is overexpressed in adenocarcinoma and squamous cell carcinomas. TET1 knockdown reduced cell growth

Yatagai N, Saito T, Akazawa Y, et al.
TP53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation.
Virchows Arch. 2019; 474(3):315-324 [PubMed] Related Publications
Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare variant of aggressive adenocarcinoma. We demonstrated previously that GAED is genetically characterized by frequent TP53 mutation. In this study, we aimed to further clarify the mechanism of inactivation of TP53 in GAED in the light of promoter methylation of TP53, and expression of methylation-associated proteins such as Ten-eleven translocation (TET) 1 and 5-hydroxymethylcytosine (5-hmc) in addition to ATM mutations. We analyzed 51 cases of GAED. The ATM mutation was detected in only one case. Promoter methylation of TP53 was detected in 18% and frequency of loss of heterozygosity (LOH) at TP53 locus was 37.2%. Reduced TET1 expression was found in 29 cases (56.9%) and was significantly associated with advanced stage (p = 0.01), lymph node metastasis (p = 0.04), and macroscopic type (p = 0.01). Reduced 5-hmc expression was found in 28 cases (54.9%) and was significantly associated with advanced stage (p = 0.01), gender (p = 0.01), tumor location (p = 0.03), tumor size (p = 0.01), and lymph node metastasis (p = 0.01). Among 9 cases with TP53 promoter methylation, reduced expression of TET1 was observed in 6 cases, and reduced expression of 5-hmc was observed in 5 cases. Reduced expression of both TET1 and 5-hmc was significantly associated with adverse clinical outcomes. In summary, promoter methylation of TP53 is partly involved in loss of p53 expression. Aberrant methylation by reduced TET1 and 5-hmc may be involved in the development of aggressive GAED.

Liu Y, Zhu H, Zhang Z, et al.
Effects of a single transient transfection of Ten-eleven translocation 1 catalytic domain on hepatocellular carcinoma.
PLoS One. 2018; 13(12):e0207139 [PubMed] Article available free on PMC after 15/04/2020 Related Publications
Tumor suppressor genes (TSGs), including Ten-eleven translocation 1 (TET1), are hypermethylated in hepatocellular carcinoma (HCC). TET1 catalytic domain (TET1-CD) induces genome-wide DNA demethylation to activate TSGs, but so far, anticancer effects of TET1-CD are unclear. Here we showed that after HCC cells were transiently transfected with TET1-CD, the methylation levels of TSGs, namely APC, p16, RASSF1A, SOCS1 and TET1, were distinctly reduced, and their mRNA levels were significantly increased and HCC cells proliferation, migration and invasion were suppressed, but the methylation and mRNA levels of oncogenes, namely C-myc, Bmi1, EMS1, Kpna2 and c-fos, were not significantly change. Strikingly, HCC subcutaneous xenografts in nude mice remained to be significantly repressed even 54 days after transient transfection of TET1-CD. So, transient transfection of TET1-CD may be a great advance in HCC treatment due to its activation of multiple TSGs and persistent anticancer effects.

Chen N, Zhao G, Yan X, et al.
A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1.
Genome Biol. 2018; 19(1):218 [PubMed] Article available free on PMC after 15/04/2020 Related Publications
BACKGROUND: Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.
RESULTS: Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation.
CONCLUSIONS: These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA.

Zhang B, Zhang X, Jin M, et al.
CagA increases DNA methylation and decreases PTEN expression in human gastric cancer.
Mol Med Rep. 2019; 19(1):309-319 [PubMed] Article available free on PMC after 15/04/2020 Related Publications
Gastric cancer is one of the leading causes of cancer-associated mortality worldwide. Cytotoxin‑associated gene A (CagA) has been reported to be associated with gastric diseases. Phosphatase and tensin homolog (PTEN) and tet methylcytosine dioxygenase 1 (Tet1) are important tumor‑suppressor genes. The present study aimed to investigate the underlying functions of CagA in human gastric cancer, and to explore the associations between CagA, PTEN and Tet1 in gastric cancer. For that purpose, CagA overexpression and Tet1 interference recombinant lentiviral plasmids were constructed. Quantitative polymerase chain reaction (qPCR) was utilized to screen gene expression in HGC‑27 human gastric cancer cells overexpressing CagA. qPCR and western blotting were used to detect gene and protein expression, respectively. In addition, the methylation status of PTEN was detected by methylation‑specific PCR. The expression levels of PTEN, Tet1, apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC)3A, APOBEC3C and APOBEC3F were significantly decreased in the CagA overexpression group compared with in the negative control group in HGC‑27 cells. Compared with in the negative control group, the mRNA and protein expression levels of PTEN were markedly decreased in cells with Tet1 interference. The decreased expression of PTEN was associated with increased methylation levels in the cells. In addition, the protein expression levels of PTEN were significantly decreased in HGC‑27 cells when CagA was overexpressed. The expression levels of PTEN and Tet1 were also markedly decreased in CagA+ gastric cancer tissues compared with in non‑cancerous tissues. The decreased expression of PTEN in CagA+ gastric cancer tissues was associated with increased methylation levels. In conclusion, overexpression of CagA significantly decreased the expression of PTEN, Tet1, APOBEC3A, APOBEC3C and APOBEC3F in human gastric cancer. In addition, CagA increased DNA methylation and decreased PTEN expression, which was reversed by Tet1 overexpression. The present study may facilitate future therapeutic approaches targeting human gastric cancer.

Huang JP, Lin J, Tzen CY, et al.
World J Gastroenterol. 2018; 24(38):4412-4418 [PubMed] Article available free on PMC after 15/04/2020 Related Publications
Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up.

Li J, Shen N, Bai GP, Huang XS
MiR-365a-3p suppresses proliferation and invasion of Hep-2 cells through targeting ten-eleven translocation 1 (TET1).
Neoplasma. 2018; 65(5):730-735 [PubMed] Related Publications
miRNAs are among the most important factors that regulate gene expression. According to bioinformatic analysis, miR-365a-3p was predicted to interact with the TET1 mRNA. We predicted that it might affect tumor biological processes through TET1. TET1 interference and miR-365a-3p inhibitor constructs were generated. qRT-PCR was used to verify the expression level of miR-365a-3p and TET1 in Hep-2 and BESB-2B cells. qRT-PCR and Western blot were used to confirm the TET1 expression level in Hep-2 and miR-365a-3p inhibitor cells. Cell proliferation, cell cycle progression and cell invasion were further studied to identify the relationship between TET1 and miR-365a-3p. Luciferase reporter gene assays were used to find the binding site of miR-365a-3p in the 3'-UTR (3'-untranslated region) of the TET1 mRNA. TET1 was weakly expressed in Hep-2 cells and highly expressed in BESB-2B cells, while miR-143-3p and miR-365a-3p were highly expressed in Hep-2 cells and lowly expressed in BESB-2B cells. Inhibiting miR-365a-3p could up-regulate the expression of TET1. The negative effects of miR-365a-3p on cell proliferation, cell cycle progression and cell invasion could be abolished by TET1 interference. The binding site of miR-365a-3p was in the 3'-UTR of the TET1 mRNA. TET1 is one of the targets of miR-365a-3p. miR-365a-3p regulates the biological behavior of laryngeal cancer by down-regulating TET1.

Xicola RM, Manojlovic Z, Augustus GJ, et al.
Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans.
Carcinogenesis. 2018; 39(11):1331-1341 [PubMed] Article available free on PMC after 13/12/2019 Related Publications
African Americans (AAs) have higher incidence and mortality rates of colorectal cancer (CRC) compared with other US populations. They present with more right-sided, microsatellite stable disease and are diagnosed at earlier ages compared with non-Hispanic Whites (NHWs). To gain insight into these trends, we conducted exome sequencing (n = 45), copy number (n = 33) and methylation analysis (n = 11) of microsatellite stable AA CRCs. Results were compared with data from The Cancer Genome Atlas (TCGA). Two of the 45 tumors contained POLE mutations. In the remaining 43 tumors, only 27 (63%) contained loss-of-function mutations in APC compared with 80% of TCGA NHW CRCs. APC-mutation-negative CRCs were associated with an earlier onset of CRC (P = 0.01). They were also associated with lower overall mutation burden, fewer copy number variants and a DNA methylation signature that was distinct from the CpG island methylator phenotype characterized in microsatellite unstable disease. Three of the APC-mutation-negative CRCs had loss-of-function mutations in BCL9L. Mutations in driver genes identified by TCGA exome analysis were less frequent in AA CRC cases than TCGA NHWs. Genes that regulate the WNT signaling pathway, including SOX9, GATA6, TET1, GLIS1 and FAT1, were differentially hypermethylated in APC-mutation-negative CRCs, suggesting a novel mechanism for cancer development in these tumors. In summary, we have identified a subtype of CRC that is associated with younger age of diagnosis, lack of APC mutation, microsatellite and chromosome stability, lower mutation burden and distinctive methylation changes.

Shenoy N, Creagan E, Witzig T, Levine M
Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly.
Cancer Cell. 2018; 34(5):700-706 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
Vitamin C (ascorbic acid, ascorbate), despite controversy, has re-emerged as a promising anti-cancer agent. Recent knowledge of intravenous ascorbate pharmacokinetics and discovery of unexpected mechanisms of ascorbate action have spawned many investigations. Two mechanisms of anti-cancer activity with ascorbate have gained prominence: hydrogen peroxide-induced oxidative stress and DNA demethylation mediated by ten-eleven translocation enzyme activation. Here, we highlight salient aspects of the evolution of ascorbate in cancer treatment, provide insights into the pharmacokinetics of ascorbate, describe mechanisms of its anti-cancer activity in relation to the pharmacokinetics, outline promising preclinical and clinical evidence, and recommend future directions.

Fan J, Zhang Y, Mu J, et al.
TET1 exerts its anti-tumor functions via demethylating DACT2 and SFRP2 to antagonize Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma cells.
Clin Epigenetics. 2018; 10(1):103 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
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 β-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/β-catenin signaling via demethylation of Wnt antagonists (DACT2 and SFRP2).

Barazeghi E, Prabhawa S, Norlén O, et al.
Decrease of 5-hydroxymethylcytosine and TET1 with nuclear exclusion of TET2 in small intestinal neuroendocrine tumors.
BMC Cancer. 2018; 18(1):764 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) originate from enterochromaffin cells scattered in the intestinal mucosa of the ileum and jejunum. Loss of one copy of chromosome 18 is the most frequent observed aberration in primary tumors and metastases. The aim of this study was to investigate possible involvement of 5-hydroxymethylcytosine (5hmC), TET1 and TET2 in SI-NETs.
METHODS: The analysis was conducted using 40 primary tumors and corresponding 47 metastases. The level of 5hmC, TET1 and TET2 was analyzed by DNA immune-dot blot assay and immunohistochemistry. Other methods included a colony forming assay, western blotting analysis, and quantitative bisulfite pyrosequencing analysis. The effect of the exportin-1 nuclear transport machinery inhibitors on cell proliferation and apoptosis was also explored using two SI-NET cell lines.
RESULTS: Variable levels of 5hmC and a mosaic staining appearance with a mixture of positive and negative cell nuclei, regardless of cell number and staining strength, was observed overall both in primary tumors and metastases. Similarly aberrant staining pattern was observed for TET1 and TET2. In a number of tumors (15/32) mosaic pattern together with areas of negative staining was also observed for TET1. Abolished expression of TET1 in the tumors did not seem to involve hypermethylation of the TET1 promoter region. Overexpression of TET1 in a colony forming assay supported a function as cell growth regulator. In contrast to 5hmC and TET1, TET2 was also observed in the cytoplasm of all the analyzed SI-NETs regardless of nuclear localization. Treatment of CNDT2.5 and KRJ-I cells with the exportin-1 (XPO1/CRM1) inhibitor, leptomycin B, induced reduction in the cytoplasm and nuclear retention of TET2. Aberrant partitioning of TET2 from the nucleus to the cytoplasm seemed therefore to involve the exportin-1 nuclear transport machinery. Reduced cell proliferation and induction of apoptosis were observed after treatment of CNDT2.5 and KRJ-I cells with leptomycin B or KPT-330 (selinexor).
CONCLUSIONS: SI-NETs are epigenetically dysregulated at the level of 5-hydroxymethylcytosine/ TET1/TET2. We suggest that KPT-330/selinexor or future developments should be considered and evaluated for single treatment of patients with SI-NET disease and also in combinations with somatostatin analogues, peptide receptor radiotherapy, or everolimus.

Liu Y, Ren X, Ke J, et al.
SC1 inhibits the differentiation of F9 embryonic carcinoma cells induced by retinoic acid.
Acta Biochim Biophys Sin (Shanghai). 2018; 50(8):793-799 [PubMed] Related Publications
The ability to self-renew is one of the most important properties of embryonic stem (ES) cells. Pluripotin (SC1), a small molecule with high activity and low toxicity, promotes self-renewal in mouse ES cells. SC1 can noticeably change the morphology of retinoic acid (RA)-induced F9 embryonic carcinoma cells (F9 cells). However, in the long term, RA and SC1 together cause cell apoptosis. When being added after 18-24 h of RA-induced F9 cell differentiation, SC1 transitorily activated Nanog and Oct4. Both Nanog and Oct4 were downregulated when SC1 and RA were added simultaneously. On the other hand, Klf4 was continually activated when SC1 was added between 6 and 24 h. Phosphorylated Erk1/2 protein levels were reduced from 6 to 24 h, whereas unphosphorylated Erk1 protein levels remained unchanged. A higher concentration of SC1 promoted cell self-renewal by strengthening the inhibition of Erk1/2 protein phosphorylation in F9 cells. Furthermore, SC1 and RA affect global DNA methylation by influencing the expressions of methylation-associated proteins, including Dnmt3b, Dnmt3l, Tet1, Tet2, and Tet3. In conclusion, SC1 inhibits the differentiation of RA-induced F9 cells mainly by reducing the levels of phosphorylated Erk1/2 and enhancing the expression of Klf4, although it also reduces DNA methylation, which may have an additional effect on ES cell differentiation.

Lubecka K, Flower K, Beetch M, et al.
Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development.
Epigenetics. 2018; 13(6):605-626 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls). Out of 22 differentially methylated loci selected for validation by pyrosequencing, 19 loci with neighbouring CpG sites (probes) were confirmed in the pre-diagnostic study group and subjected to verification in a prospective cirrhotic cohort (13 cases, 23 controls). We established for the first time 9 probes that could distinguish HBV-negative cirrhotic patients who subsequently developed HCC from those who stayed cancer-free. These probes were identified within regulatory regions of BARD1, MAGEB3, BRUNOL5, FXYD6, TET1, TSPAN5, DPPA5, KIAA1210, and LSP1. Methylation levels within DPPA5, KIAA1210, and LSP1 were higher in prospective samples from HCC cases vs. cirrhotic controls. The remaining probes were hypomethylated in cases compared with controls. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established probes have potential to be developed into a routine clinical test after validation in larger cohorts.

Bai M, Yang L, Liao H, et al.
Metformin sensitizes endometrial cancer cells to chemotherapy through IDH1-induced Nrf2 expression via an epigenetic mechanism.
Oncogene. 2018; 37(42):5666-5681 [PubMed] Related Publications
Chemoresistance is the major obstacle to cure endometrial cancer, whereas metformin has demonstrated sensitization to chemotherapy in endometrial cancer. A novel finding states that isocitrate dehydrogenase 1 (IDH1) involves in cancer chemoresistance. Recent studies have revealed that epigenetic modifications facilitate chemoresistance. However, whether IDH1 play a role in metformin-induced endometrial cancer chemosensitivity through epigenetic modification is incompletely understood. Immunohistochemistry and Elisa assays were used to evaluate the expression pattern of IDH1 in endometrial tissue and serum, respectively. Western blot was performed to determine changes in expression of key molecules in the IDH1-ɑ-KG-TET1-Nrf2 signaling pathway after various treatments. Dot blot assays were used to assess global hydroxymethylation levels after metformin administration or plasmid transfection. Antioxidant response element (ARE) activity in the IDH1 promoter region was monitored by luciferase assay. Cancer cell sensitivity to chemotherapy was detected by SRB assay. We found that activation of the IDH1 signaling pathway in endometrial cancer tissue resulting from aberrant expression of IDH1 and its downstream mediators conferred chemoresistance. We found that this effect was abated by metformin treatment. Dot blot and HMeDIP assays revealed that metformin blocked IDH1-ɑ-KG-TET1-mediated enhancement of Nrf2 hydroxymethylation levels, eliminating chemoresistance. Moreover, we observed that chemoresistance was enhanced via a regulatory loop in which Nrf2 activated IDH1-ɑ-KG-TET1-Nrf2 signaling via binding to the ARE sites in the IDH1 promoter region. Our findings highlight a critical role of IDH1-ɑ-KG-TET1-Nrf2 signaling in chemoresistance and suggest that rational combination therapy with metformin and chemotherapeutics has the potential to suppress chemoresistance.

Good CR, Panjarian S, Kelly AD, et al.
TET1-Mediated Hypomethylation Activates Oncogenic Signaling in Triple-Negative Breast Cancer.
Cancer Res. 2018; 78(15):4126-4137 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
Both gains and losses of DNA methylation are common in cancer, but the factors controlling this balance of methylation remain unclear. Triple-negative breast cancer (TNBC), a subtype that does not overexpress hormone receptors or HER2/NEU, is one of the most hypomethylated cancers observed. Here, we discovered that the TET1 DNA demethylase is specifically overexpressed in about 40% of patients with TNBC, where it is associated with hypomethylation of up to 10% of queried CpG sites and a worse overall survival. Through bioinformatic analyses in both breast and ovarian cancer cell line panels, we uncovered an intricate network connecting TET1 to hypomethylation and activation of cancer-specific oncogenic pathways, including PI3K, EGFR, and PDGF. TET1 expression correlated with sensitivity to drugs targeting the PI3K-mTOR pathway, and CRISPR-mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes, and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression. Our work establishes TET1 as a potential oncogene that contributes to aberrant hypomethylation in cancer and suggests that TET1 could serve as a druggable target for therapeutic intervention.

Dziaman T, Gackowski D, Guz J, et al.
Characteristic profiles of DNA epigenetic modifications in colon cancer and its predisposing conditions-benign adenomas and inflammatory bowel disease.
Clin Epigenetics. 2018; 10:72 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
Background: Active demethylation of 5-methyl-2'-deoxycytidine (5-mdC) in DNA occurs by oxidation to 5-(hydroxymethyl)-2'-deoxycytidine (5-hmdC) and further oxidation to 5-formyl-2'-deoxycytidine (5-fdC) and 5-carboxy-2'-deoxycytidine (5-cadC), and is carried out by enzymes of the ten-eleven translocation family (TETs 1, 2, 3). Decreased level of epigenetic DNA modifications in cancer tissue may be a consequence of reduced activity/expression of TET proteins. To determine the role of epigenetic DNA modifications in colon cancer development, we analyzed their levels in normal colon and various colonic pathologies. Moreover, we determined the expressions of TETs at mRNA and protein level.The study included material from patients with inflammatory bowel disease (IBD), benign polyps (AD), and colorectal cancer (CRC). The levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in examined tissues were determined by means of isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS). The expressions of
Results: IBD was characterized by the highest level of 8-oxodG among all analyzed tissues, as well as by a decrease in 5-hmdC and 5-mdC levels (at a midrange between normal colon and CRC). AD had the lowest levels of 5-hmdC and 5-mdC of all examined tissues and showed an increase in 8-oxodG and 5-(hydroxymethyl)-2'-deoxyuridine (5-hmdU) levels. CRC was characterized by lower levels of 5-hmdC and 5-mdC, the lowest level of 5-fdC among all analyzed tissues, and relatively high content of 5-cadC. The expression of
Conclusions: Our findings suggest that a complex relationship between aberrant pattern of DNA epigenetic modification and cancer development does not depend solely on the transcriptional status of TET proteins, but also on the characteristics of premalignant/malignant cells. This study showed for the first time that the examined colonic pathologies had their unique epigenetic marks, distinguishing them from each other, as well as from normal colonic tissue. A decrease in 5-fdC level may be a characteristic feature of largely undifferentiated cancer cells.

Kawai H, Matsushita H, Aoyama Y, et al.
Dysplastic features seen in a patient with acute myeloid leukemia harboring the KTM2A-TET1 fusion gene.
Int J Hematol. 2018; 108(1):1-2 [PubMed] Related Publications

Kang KA, Ryu YS, Piao MJ, et al.
DUOX2-mediated production of reactive oxygen species induces epithelial mesenchymal transition in 5-fluorouracil resistant human colon cancer cells.
Redox Biol. 2018; 17:224-235 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT. First, we showed that 5-FU-resistant SNUC5 colon cancer cells (SNUC5/FUR cells) undergo EMT by analyzing the expression of EMT markers such as N-cadherin, vimentin and E-cadherin. In addition, we found that the resistant cells expressed higher levels of Snail, Slug, Twist and Zeb1, which are all critical EMT regulators and had enhanced migratory and invasive capabilities. Furthermore, SNUC5/FUR cells had increased level of DUOX2, resulting in increased ROS level. This effect was due to the enhanced binding of the ten eleven translocation 1 (TET1) demethylase to the DUOX2 promoter in the SNUC5/FUR cells. Importantly, silencing of TET1 reversed the effects of 5-FU on the cells. Finally, the antioxidant N-acetylcysteine attenuated the effects of 5-FU on EMT and metastasis. Our study demonstrates the existence of a TET1/DUOX2/ROS/EMT axis that could play a role in colon cancer chemo-resistance and the aggressiveness of this cancer.

Fu R, Ding Y, Luo J, et al.
Ten-eleven translocation 1 regulates methylation of autophagy-related genes in human glioma.
Neuroreport. 2018; 29(9):731-738 [PubMed] Related Publications
Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and is related to the malignant biological behavior of tumors. However, its regulatory role in glioma remains unclear. In this study, the levels of 5mC and 5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western blot in glioma tissues and normal brain tissues, whereas 5hmC differentially enriched genes were determined and further validated. The level of 5hmC in gliomas was decreased, whereas 5mC was increased. 5hmC highly enriched 10 functional protein-coding genes and 10 signaling pathways were identified using hMeGIP-chip in glioma tissues. Two autophagy-related genes, ATG13 and DNA damage-regulated autophagy modulator protein 1, with low enrichment of 5hmC in glioma tissues were verified in the promoter region, and hMeGIP-PCR further confirmed this result in U251 cells. Immunohistochemistry further confirmed that autophagy level in glioma tissues was lower than that of normal controls, and negatively correlated with WHO grade. This study indicates that ten-eleven translocation 1 may be involved in the development and progression of glioma through demethylation regulating a variety of cellular functions and signaling pathways, and autophagy is one of the regulatory mechanisms.

Bezerra Salomão K, Cruzeiro GAV, Bonfim-Silva R, et al.
Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups.
J Neurooncol. 2018; 139(1):33-42 [PubMed] Related Publications
INTRODUCTION: Medulloblastoma (MB) is an embryonal tumour that originates from genetic deregulation of cerebellar developmental pathways and is classified into 4 molecular subgroups: SHH, WNT, group 3, and group 4. Hydroxymethylation levels progressively increases during cerebellum development suggesting a possibility of deregulation in MB pathogenesis. The aim of this study was to investigate global hydroxymethylation levels and changes in TET and IDH gene expression in MB samples compared to control cerebellum samples.
METHODS: The methods utilized were qRT-PCR for gene expression, dot-blot and immunohistochemistry for global hydroxymethylation levels and sequencing for the investigation of IDH mutations.
RESULTS: Our results show that global hydroxymethylation level was decreased in MB, and low 5hmC level was associated with the presence of metastasis. TET1 expression levels were decreased in the WNT subgroup, while TET3 expression levels were decreased in the SHH subgroup. Reduced TET3 expression levels were associated with the presence of events such as relapse and death. Higher expression of IDH1 was observed in MB group 3 samples, whereas no mutations were detected in exon 4 of IDH1 and IDH2.
CONCLUSION: These findings suggest that reduction of global hydroxymethylation levels, an epigenetic event, may be important for MB development and/or maintenance, representing a possible target in this tumour and indicating a possible interaction of TET and IDH genes with the developmental pathways specifically activated in the MB subgroups. These genes could be specific targets and markers for each subgroup.

Zhou Y, Zheng X, Lu J, et al.
Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.
Cell Physiol Biochem. 2018; 45(6):2548-2559 [PubMed] Related Publications
BACKGROUND/AIMS: The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown.
METHODS: microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production.
RESULTS: Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host gene. 20(S)-Rg3 inhibited DNMT3A expression while exerted insignificant effect on DNMT1, DNMT3B and TET1-3. 20(S)-Rg3 reversed DNMT3A-mediated methylation in the promoter of the host gene of miR-532-3p, and thus elevated miR-532-3p level followed by suppression of HK2 and PKM2 expression, glucose consumption and lactate production.
CONCLUSIONS: 20(S)-Rg3 modulated microRNAs to exert the anti-tumor effect in ovarian cancer. 20(S)-Rg3 lessened the DNMT3A-mediated methylation and promoted the suppression of miR-532-3p on HK2 to antagonize the Warburg effect of ovarian cancer cells.

Cheng YW, Chou CJ, Yang PM
Ten-eleven translocation 1 (TET1) gene is a potential target of miR-21-5p in human colorectal cancer.
Surg Oncol. 2018; 27(1):76-81 [PubMed] Related Publications
DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world. However, the involving molecular mechanisms are still unclear. The oncogenic microRNA (miRNA) miR-21-5p has recently identified as a diagnostic and prognostic biomarker in CRC. In this study, TET1 was predicted as a novel target of miR-21-5p by using a web-based predictive software starBase v2.0. We found that the 3'-UTR region of TET1 gene contains a miR-21-5p-binding site. Examination of tumor tissues from CRC patients found that loss of TET1 was associated with the progression of CRC to advance stages. In addition, negative correlation of miR-21-5p and TET1 expression was also observed. Transfection of the synthetic miR-21-5p mimic or inhibitor into the colorectal cancer cells could inhibit or increase the TET1-3'-UTR luciferase activity, respectively. Our results demonstrate that TET1 is a potential target of miR-21-5p in CRC.

Lasho TL, Vallapureddy R, Finke CM, et al.
Infrequent occurrence of TET1, TET3, and ASXL2 mutations in myelodysplastic/myeloproliferative neoplasms.
Blood Cancer J. 2018; 8(3):32 [PubMed] Article available free on PMC after 12/11/2019 Related Publications

Li Y, Shen Z, Jiang H, et al.
MicroRNA‑4284 promotes gastric cancer tumorigenicity by targeting ten-eleven translocation 1.
Mol Med Rep. 2018; 17(5):6569-6575 [PubMed] Article available free on PMC after 12/11/2019 Related Publications
Increasing evidence has shown that abnormal expression of miR-4284 participates in the progression of several types of cancer. However, the expression and the role of miR‑4284 in gastric cancer remain largely unknown. Therefore, in the present study the miR‑4284 expression levels in gastric cancer tissues and cell lines, was examined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and found that miR‑4284 was significantly upregulated in 40 pairs of gastric cancer tissues and five gastric cancer cell lines compared to the corresponding normal tissues and GES‑1 cell line. In addition, increased miR‑4284 expression was positively associated with TNM stage (P=0.035), distal metastasis (P=0.022) and poor prognosis in gastric cancer patients. Furthermore, the overexpression of miR‑4284 expression was shown to promote cell proliferation, clone formation, invasion and migration, while the suppression of miR‑4284 expression induced opposite effects. Additionally, luciferase reporter assay was conducted and showed that ten-eleven translocation 1 (TET1), a tumor suppressor gene that regulating cell survival and metastasis, was a direct target of miR‑4284. Upregulated miR‑4284 decreased the mRNA and protein levels of TET1 in SGC‑7901 cells and downregulated miR‑4284 increased the mRNA and protein levels of TET1 in AGS cells. In addition, miR‑4284 expression was negatively correlated with the TET1 expression in gastric cancer tissues. Moreover, inhibition of TET1 suppressed the effect of miR‑4284 inhibitors on cell proliferation in AGS cells. Therefore, data demonstrated that miR‑4284 could promote tumor cell growth, migration and invasion by directly targeting TET1 in gastric cancer, which may provide a potential therapeutic target for gastric cancer treatment.

Liu J, Li M, Liu X, et al.
miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1.
Int J Oncol. 2018; 52(4):1295-1304 [PubMed] Related Publications
Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR‑27a‑3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR‑27a‑3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR‑27a‑3p in the development and progression of osteosarcoma, the expression of miR‑27a‑3p was inhibited by transfection of the MG-63 cells with miR‑27a‑3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and α-catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR‑27a‑3p recognized the TET1 3'-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR‑27a‑3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR‑27a‑3p. Taken together, the findings of this study indicate that miR‑27a‑3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR‑27a‑3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR‑27a‑3p/TET1 may thus be a potential target for the treatment of osteosarcoma.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. TET1, Cancer Genetics Web: http://www.cancer-genetics.org/LCX.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 31 August, 2019     Cancer Genetics Web, Established 1999