NAD Modulates DNA Methylation and Cell Differentiation

Ummarino, Simone; Hausman, Clinton; Gaggi, Giulia; Rinaldi, Lucrezia; Bassal, Mahmoud A.; Zhang, Yanzhou; Seelam, Andy Joe; Kobayashi, I; Borchiellini, Marta; Ebralidze, Alexander K.; Ghinassi, Barbara; Trinh, Bon Q.; Kobayashi, Susumu; Ruscio, Annalisa Di

doi:10.3390/cells10112986

Cited by 16 publications

(12 citation statements)

References 51 publications

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“…NAD + has been reported to enhance DNA demethylation ( 57 ). NAD + is also a substrate for polyribose polymerase 1 (PARP1), a nuclear protein that plays a key role in DNA methylation ( 58 ). Tumor NAD metabolism mainly regulates DNA demethylation through Tet1-mediated Dnmts, and NAD metabolism regulates and induces PD-L1 expression by controlling DNA demethylation ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis

Cai

Lin

et al. 2022

J Gastrointest Oncol

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Background: Because stomach adenocarcinoma (STAD) has a poor prognosis, it is necessary to explore new prognostic genes to stratify patients to guide existing individualized treatments.Methods: Survival and clinical information, RNA-seq data and mutation data of STAD were acquired from The Cancer Genome Atlas (TCGA) database. Fifty-one nicotinamide adenine dinucleotide (NAD + ) metabolism-related genes (NMRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Differentially expressed NMRGs (DE-NMRGs) between STAD and normal samples were screened, and consistent clustering analysis of STAD patients was performed based on the DE-NMRGs. Survival analysis, Gene Set Enrichment Analysis (GSEA), mutation frequency analysis, immune microenvironment analysis and drug prediction were performed among different clusters.Additionally, the differentially expressed genes (DEGs) among different clusters were selected, and the intersections of DEGs and DE-NMRGs were selected as the prognostic genes. Finally, quantitative realtime polymerase chain reaction (qRT-PCR) was performed on a human gastric mucosa epithelial cell line and cancer cell line to verify the expression of the prognostic genes.Results: A total of 27 DE-NMRGs and two clusters were selected. There was a difference in survival between clusters 1 and 2. Furthermore, 18 DE-NMRGs were significantly different between clusters 1 and 2. The different Gene Ontology (GO) biological processes and KEGG pathways between clusters 1 and 2 were mainly enriched in cyclic nucleotide mediated signaling, synaptic signaling and hedgehog signaling pathway, etc. The somatic mutation frequencies were different between the two clusters, and TTN was the highest mutated gene in the patients of the clusters 1 and 2. Additionally, eight immune cells, immune score, stromal score, and estimate score were different between clusters 1 and 2. The patients in cluster 2 were sensitive to CTLA4 inhibitor treatment. Furthermore, the top five drugs (AP.24534, BX.795, Midostaurin, WO2009093927 and CCT007093) were significantly higher in cluster 1 than in cluster 2. Finally, three genes (AOX1, NNMT and PTGIS) were acquired as prognostic, and their expressions were consistent with the results of bioinformatics analysis.Conclusions: Three prognostic genes related to NAD + metabolism in STAD were screened out, which provides a theoretical basis and reference value for future treatment and prognosis of STAD.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis

Cai

Lin

et al. 2022

J Gastrointest Oncol

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“…PARP1 can be activated by multiple stimuli, including but not limited to, DNA damage, ERK1/2 [ 24 ], hormones [ 25 ], JIL-1 [ 26 ] and NAD + [ 27 ]. The activated PARP1 forms long and branched PAR chains mainly to its auto-modification domain but also to other acceptor proteins, such as histones, chromatin regulators and transcription factors.…”

Section: Parp1 Structure and Activationmentioning

confidence: 99%

“…For example, the interaction of PARP1 with TET2 stimulates conversion of 5mC to 5hmC, which is crucial for early-stage epigenetic modification during somatic cell reprogramming [ 98 ]. NAD + supplementation stimulates PARP1 activity and produced PAR that inhibits DNMT1 activity, resulting in demethylation and transcriptional activation of the CEBPA gene that may be related to myeloid differentiation [ 27 ]. Hyperactivation of PARP1 is associated with impaired DNA methylation processes in peripheral blood mononuclear cells from type 2 diabetes mellitus patients [ 99 ].…”

Section: Parp1 As a Modulator Of Dna Methylationmentioning

confidence: 99%

PARP1: Liaison of Chromatin Remodeling and Transcription

Zong

Gong

Sun

et al. 2022

Cancers

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Poly(ADP-ribosyl)ation (PARylation) is a covalent post-translational modification and plays a key role in the immediate response of cells to stress signals. Poly(ADP-ribose) polymerase 1 (PARP1), the founding member of the PARP superfamily, synthesizes long and branched polymers of ADP-ribose (PAR) onto acceptor proteins, thereby modulating their function and their local surrounding. PARP1 is the most prominent of the PARPs and is responsible for the production of about 90% of PAR in the cell. Therefore, PARP1 and PARylation play a pleotropic role in a wide range of cellular processes, such as DNA repair and genomic stability, cell death, chromatin remodeling, inflammatory response and gene transcription. PARP1 has DNA-binding and catalytic activities that are important for DNA repair, yet also modulate chromatin conformation and gene transcription, which can be independent of DNA damage response. PARP1 and PARylation homeostasis have also been implicated in multiple diseases, including inflammation, stroke, diabetes and cancer. Studies of the molecular action and biological function of PARP1 and PARylation provide a basis for the development of pharmaceutic strategies for clinical applications. This review focuses primarily on the role of PARP1 in the regulation of chromatin remodeling and transcriptional activation.

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“…In several cases, the methylation of DNA by cytosine residues stop its binding to specifically reacting with proteins that carry out several genetic procedures, such as replication, transcription, as well as DNA repair [25,26]. The so-called m 5 SrG DNA-binding proteins, which are specifically located on the DNA of complex protein complexes, control and express genes [27].…”

Section: Methylation Of Dna -An Epigenetic Mechanism For Monitoring T...mentioning

confidence: 99%

Epigenetics is Promising Direction in Modern Science

Фартушок

Kovalishin

Fedevych

et al. 2021

Chemistry-Didactics-Ecology-Metrology

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Epigenetics studies the inherited changes in a phenotype or in expression of genes caused by other mechanisms, without changing the nucleotide sequence of DNA. The most distinguished epigenetic tools are: modifications of histones, enzymatic DNA methylation, and gene silencing mediated by small RNAs (miRNA, siRNA). The resulting m5C residues in DNA substantially affect the cooperation of proteins with DNA. It is organized by hormones and aging-related alterations, one of the mechanisms controlling sex and cellular differentiation. DNA methylation regulates all genetic functions: repair, recombination, DNA replication, as well as transcription. Distortions in DNA methylation and other epigenetic signals lead to diabetes, premature aging, mental dysfunctions, and cancer.

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NAD Modulates DNA Methylation and Cell Differentiation

Cited by 16 publications

References 51 publications

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis

PARP1: Liaison of Chromatin Remodeling and Transcription

Epigenetics is Promising Direction in Modern Science

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