Ten–eleven translocase: key regulator of the methylation landscape in cancer

Shekhawat, Jyoti; Gauba, Kavya; Gupta, Shruti; Choudhury, Bikram; Purohit, Purvi; Sharma, Praveen; Banerjee, Mithu

doi:10.1007/s00432-021-03641-3

Cited by 20 publications

(13 citation statements)

References 92 publications

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“…VC is a epigenetic modulator involved in the reprogramming of hydroxylase cells and ten-eleven translocation (TET) proteins ( 55 , 56 ). Three members were included in the TET family: TET 1, TET 2, and TET 3, which belong to alpha-ketoglutaric acid and Fe ( 2+ )-dependent dioxygenase superfamily ( 57 , 58 ). TET proteins played an important role in the regulation of DNA demethylation through converting 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC), and 5-carboxylcytosine (5 caC), which was iron (Fe 2+ ) and 2-ketoglutarate-dependent ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…Three members were included in the TET family: TET 1, TET 2, and TET 3, which belong to alpha-ketoglutaric acid and Fe ( 2+ )-dependent dioxygenase superfamily ( 57 , 58 ). TET proteins played an important role in the regulation of DNA demethylation through converting 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC), and 5-carboxylcytosine (5 caC), which was iron (Fe 2+ ) and 2-ketoglutarate-dependent ( 58 ). Ascorbic acid could regulate the conversion of Fe 3+ to Fe 2+ ( 53 ), thus playing a catalytic role of this TET-mediated oxidation of 5mC, and provide unique capacity of regulating the dynamics of DNA methylation ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

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Vitamin C Intake and Cancers: An Umbrella Review

et al. 2022

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Based on the existing systematic reviews and meta-analyses, we conducted this umbrella review aiming at evaluating the quality of evidence, validity and biases of the relationship between vitamin C (VC) intake and incidence and outcomes of multiple cancers. We identified 22 cancer outcomes within 3,562 articles. VC consumption was associated with lower incidence of bladder cancer, breast cancer, cervical tumors, endometrial cancer, esophageal cancer, gastric cancer, glioma, lung cancer, pancreatic cancer, prostate cancer, renal cell cancer, and total cancer occurrence. VC intake was also related to decreased risk of breast cancer prognosis (recurrence, cancer-specific mortality, and all-cause mortality).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin C Intake and Cancers: An Umbrella Review

et al. 2022

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“…Recent studies have reported that 5-hmC may be associated with human cancer [ 22 , 23 ]. In the present study, the 5-hmC level of the hub genes in CRC patients was different from that in healthy patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of a 5-Hydroxymethylation Signature in Circulating Cell-Free DNA for the Noninvasive Detection of Colorectal Cancer

Liu

Tang

Zhang

et al. 2022

Journal of Oncology

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Background. As a crucial epigenetic modification, DNA 5-hydroxymethylcytosine (5-hmC) plays a key role during colorectal cancer (CRC) carcinogenesis. Nevertheless, the levels of 5-hmC-related genes in the circulating DNA of CRC remain largely unknown. Methods and Results. The GSE81314 dataset from the Gene Expression Omnibus (GEO), which was generated by chemical marking-based low-input shotgun sequencing to detect 5-hmC in circulating cell-free DNA (cfDNA) was used in the present study. The GSE81314 dataset includes data for 8 plasma samples from healthy individuals and 4 plasma samples from CRC patients. The difference in the 5-hmC levels in cfDNA between the CRC group and healthy individuals was analyzed by the differentially expressed genes (DEG) package. Weighted gene coexpression network analysis (WGCNA) was conducted to analyze gene coexpression modules associated with sample characteristics. DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes. WGCNA showed that the pink, purple, and brown modules, which contain 531 genes in total, were significantly correlated with CRC (0.66, 0.61, and -0.59, respectively). We used gene set enrichment analysis (GSEA) software to compare 5-hmC-related genes and pathways between CRC patients and healthy controls. We further performed a protein–protein interaction (PPI) analysis and identified 4 nodes (LCN2, LRG1, S100P, and TACSTD2) that played key roles in the network, and we analyzed the expression of these nodes S100P in the GEPIA database. Consistent with the 5-hmC levels in CRC patient plasma, our external validation results from the GEPIA and UALCAN databases showed that LCN2, LRG1, S100P, and TACSTD2 were highly expressed in CRC tissue compared with controls. The DNA promoter methylation levels of LCN2, LRG1, and S100P were lower in CRC tissue than in normal control tissue. Conclusion. The present findings suggest that abnormality in cell-free DNA hydroxylation in plasma may be associated with CRC. In addition, the 5-hmC levels of LCN2, LRG1, S100P, and TACSTD2 in circulating cfDNA may be used as potential noninvasive markers for CRC.

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“…In 1972, Penn et al also found hydroxylated modified cytosines in DNA extracted from brain tissues of rats, mice, and oviparous bullfrogs, which accounted for approximately 15% of the total cytosine of DNA (8). TET1, a member of the TET protein family, is an a-ketoglutarate and Fe2+-dependent dioxygenase that converts 5-methylcytosine (5m C) into 5hydroxymethylcytosine (5hm C), thereby initiating the DNA demethylation program (9,10). It was found that the downregulation of TET1 led to hypermethylation of DKK-1 promoter, activation of Wnt signaling pathway, and thus promoted the expression of Fas ligand (FasL), which led to the enhancement of immune regulation ability of periodontal ligament stem cells (11).…”

Section: Introductionmentioning

confidence: 99%

MiR-27a-3p binds to TET1 mediated DNA demethylation of ADCY6 regulates breast cancer progression via epithelial-mesenchymal transition

et al. 2022

Front. Oncol.

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IntroductionAdenylyl cyclase isoform 6 (ADCY6) is a member of membrane-bound adenylate cyclase family that converts adenosine triphosphate (ATP) into cAMP and pyrophosphate. An increasing number of researchers have studied the role of ADCY6 in cancer. However, its specific role in breast cancer remains unknown.MethodsBioinformatics and clinical data were used to analyse the expression of ADCY6 in breast cancer. ADCY6 DNA methylation was analysed using DNA methylation-specific PCR and Bisulfite Sanger sequencing. Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between miR-27a-3p, TET1 and ADCY6 in breast cancer.ResultsWe found that ADCY6 is expressed at low levels in breast cancer and leads to increases in the proliferation, invasion and migration of breast cancer cells. The low expression of ADCY6 is due to the lower demethylation of ten-eleven translocation methylcytosine dioxygenase 1 (TET1), and the methylation of ADCY6 can be altered by TET1. More importantly, bioinformatics analysis showed that TET1 is regulated by miR-27a-3p and regulates the methylation of ADCY6 to affect the EMT process of breast cancer cells, thereby affecting the malignant biological behaviour of breast cancer.ConclusionsOur study demonstrates that the methylation modification of ADCY6 is regulated by TET1 and leads to ADCY6 activation. miR-27a-3p negatively regulates the expression of TET1 and affects the EMT process of breast cancer through ADCY6, thereby promoting the malignant biological behaviour of breast cancer. Our results may provide new research ideas and directions for DNA methylation and EMT changes in breast cancer.

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Ten–eleven translocase: key regulator of the methylation landscape in cancer

Cited by 20 publications

References 92 publications

Vitamin C Intake and Cancers: An Umbrella Review

Vitamin C Intake and Cancers: An Umbrella Review

Identification of a 5-Hydroxymethylation Signature in Circulating Cell-Free DNA for the Noninvasive Detection of Colorectal Cancer

MiR-27a-3p binds to TET1 mediated DNA demethylation of ADCY6 regulates breast cancer progression via epithelial-mesenchymal transition

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