Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

Xu, Xuehe; Watt, David S.; Liu, Chunming

doi:10.1093/abbs/gmv083

Cited by 14 publications

(10 citation statements)

References 78 publications

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“…TDG encodes thymine DNA glycosylase, which participates in active DNA demethylation in the mammalian genome 35,36 . Therefore, decreased TDG levels may induce the accumulation of 5-hydroxymethylcytosine, 5-carboxylcytosine, and 5-formylcytosine 35,36 , which may lead to genomic instability and the occurrence of malignancy 41 . For instance, previous studies have reported that low levels of TDG expression are associated with poor prognosis in breast cancer (HR = 2.178, 95% confidence interval: 1.140-4.163, p = 0.018) 42 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3′-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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“…All these observations hint to a functional interplay between DNA methylation and demethylation processes to provide locus-specific epigenetic plasticity that allows post-developmental somatic cells to regulate transcriptional activity in response to environmental and systemic cues. Notably, TDG was shown to physically interact with variety of nuclear receptors, transcription factors and chromatin-regulating proteins as well as with DNMTs [8,126], indicating a central role in controlling DNA methylation states at regulatory regions of poised or active genes. Consistently, targeting TDG as well as TET proteins to silent genes was shown to effect DNA methylation changes and reactivate transcription [127,128].…”

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confidence: 99%

Active DNA demethylation by DNA repair: Facts and uncertainties

2016

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Pathways that control and modulate DNA methylation patterning in mammalian cells were poorly understood for a long time, although their importance in establishing and maintaining cell type-specific gene expression was well recognized. The discovery of proteins capable of converting 5-methylcytosine (5mC) to putative substrates for DNA repair introduced a novel and exciting conceptual framework for the investigation and ultimate discovery of molecular mechanisms of DNA demethylation. Against the prevailing notion that DNA methylation is a static epigenetic mark, it turned out to be dynamic and distinct mechanisms appear to have evolved to effect global and locus-specific DNA demethylation. There is compelling evidence that DNA repair, in particular base excision repair, contributes significantly to the turnover of 5mC in cells. By actively demethylating DNA, DNA repair supports the developmental establishment as well as the maintenance of DNA methylation landscapes and gene expression patterns. Yet, while the biochemical pathways are relatively well-established and reviewed, the biological context, function and regulation of DNA repair-mediated active DNA demethylation remains uncertain. In this review, we will thus summarize and critically discuss the evidence that associates active DNA demethylation by DNA repair with specific functional contexts including the DNA methylation erasure in the early embryo, the control of pluripotency and cellular differentiation, the maintenance of cell identity, and the nuclear reprogramming.

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“…The methylation and demethylation of genomic DNA are important aspects of epigenetics, and two processes keeping balance each other to maintain the stability of methylation profiles. The TDG gene plays an important role in DNA repair, DNA demethylation, and transcription regulation and influences embryonic development and tumorigenesis [14]. Under natural conditions and accelerated oocyte aging conditions, the dynamic changes in the DNA demethylation of mouse oocytes under aging conditions are associated with TET3 gene over-expression and TDG inhibition [15].…”

Section: Discussionmentioning

confidence: 99%

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Zhang

Liu²,

Zhu³

et al. 2016

Cell Physiol Biochem

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Aims: To study the effect of thymine DNA glycosylase (TDG) gene knockdown on the differentiation of pig preadipocytes. Methods: Preadipocytes were obtained from subcutaneous adipose tissue from the neck of 1- to 7-day-old pigs. The TDG gene was knocked down using siRNA, and cell differentiation was induced. The mRNA expression level was measured using fluorescence quantitative PCR, and the protein expression level was determined using Western blot analysis. The DNA methylation levels in promoter regions of differentiation-related genes were also evaluated. Results: TDG gene knockdown decreased the mRNA expression levels of the peroxisome proliferator-activated receptorγ (PPARγ) and Fatty acid binding proteins 4(FABP4 Also known as aP2) genes (P<0.01), while the mRNA expression level of the CCAAT/enhancer binding protein alpha(C/EBPα) gene did not change significantly (P>0.05). In addition, after induced differentiation, the lipid droplet production significantly decreased, and the percentages of methylation in the promoter regions of C/EBPα, PPARγ, and aP2 genes were 0.9%, 80%, and 76%, respectively. In contrast, the percentages of methylation in the negative control groups were 0.5%, 67.5%, and 58%, respectively. Conclusion: TDG gene knockdown could inhibit the differentiation of pig preadipocytes and affect the DNA methylation levels of some transcription factors.

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Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis

Cited by 14 publications

References 78 publications

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Active DNA demethylation by DNA repair: Facts and uncertainties

Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

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