DNA hydroxymethylation increases the susceptibility of reactivation of methylated <i>P16</i> alleles in cancer cells

Li, Paiyun; Gan, Ying; Qin, Sisi; Han, Xiao; Cui, Chenghua; Liu, Zhaojun; Zhou, Jing; Gu, Lin; Lu, Zheming; Zhang, Baozhen; Deng, Dajun

doi:10.1080/15592294.2019.1700004

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…The mRNA expression level was upregulated in CRC tissue, which was associated with a poor prognosis in CRC patients. It is reported that DNA hydroxymethylation increases the susceptibility to reactivation of methylated P16 alleles in cancer cells, and 5-hmc may play an important role in gene transcription [ 37 ]. This may partly explain our research that LCN2, LRG1, S100P, and TACSTD2 DNA hydroxymethylation levels were positively correlated with their mRNA levels.…”

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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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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“…The aberrant methylation and demethylation have been linked to pathogenesis of diseases, such as cancers, neurodegenerative disorders, and others (heart, liver, kidney, lung, and immunological disorders) [34][35][36][37]. Of the main components in the machinery for cytosine modifications, TET family members shape the landscape of the epigenome via regulation and disposition of 5-hmC levels [38,39] and distinctly function as regulators for brain development as well as suppressors and promoters for tumorigenesis [26,[40][41][42][43][44][45][46] (Tables 1,2,3,4, Ref. [15,[34][35][36][37]).…”

Section: Common Chemical Functions Of Tet Proteins Referencesmentioning

confidence: 99%

Ten-eleven translocation proteins (TETs): tumor suppressors or tumor enhancers?

Seong

Liu

et al. 2021

Front. Biosci. (Landmark Ed)

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The epigenetic memory stored in the dynamic modifications, such as base modifications of cytosine (C) in DNA, including methylation/hydroxymethylation/demethylation, causes heritable phenotypes via regulating gene expression without alteration of DNA sequence. The process from cytosine modification to the epigenetic effect is orchestrated by complicated machinery consisting of writers, erasers, readers, and other factors. The two major forms of cytosine modification include methylcytosine (5-mC) and hydroxymethylcytosine (5-hmC). DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B function as writers for 5-mC. The ten-eleven translocation proteins (TET) including TET1, TET2, and TET3 in the mammalian genome are responsible for hydroxymethylation of 5-mC to generate 5-hmC, 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC). The 5-mC and 5-hmC have become the two most extensively investigated epigenetic markers, and the dynamic balance of these two markers shape the landscape of the epigenome, functioning as a platform to regulate gene expression epigenetically. The landscape of the 5-hmC in epigenome is precisely and tightly regulated during the development. Aberrant alterations of the epigenetic regulation may cause severe consequences such as phenotype change as well as initiation of disease. Progressively, significant achievements have been made in characterization of writers, erasers, and readers of 5-mC and 5-hmC, as well as the contribution of aberrant alteration of 5-hmC/5-mC landscape to the pathogenesis of human diseases, such as cancers and neurological disorders. This article will highlight the research advances in the distinct contribution of TET proteins as suppressors or promoters to the pathogenesis of tumorigenesis and progression. Furthermore, this article also discusses the challenges and the directions for research in the future.

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Marqueurs d’oxydation des acides nucléiques

Baudin

2020

Revue Francophone des Laboratoires

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DNA hydroxymethylation increases the susceptibility of reactivation of methylated P16 alleles in cancer cells

Cited by 4 publications

References 41 publications

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

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

Ten-eleven translocation proteins (TETs): tumor suppressors or tumor enhancers?

Marqueurs d’oxydation des acides nucléiques

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