Butyrate Drives Metabolic Rewiring and Epigenetic Reprogramming in Human Colon Cancer Cells.


Journal

Molecular nutrition & food research
ISSN: 1613-4133
Titre abrégé: Mol Nutr Food Res
Pays: Germany
ID NLM: 101231818

Informations de publication

Date de publication:
06 2022
Historique:
revised: 23 03 2022
received: 11 01 2022
pubmed: 17 4 2022
medline: 23 6 2022
entrez: 16 4 2022
Statut: ppublish

Résumé

Butyrate (B) is a short-chain fatty acid produced by dietary fiber, known to inhibit histone deacetylases (HDACs) and possess cancer-preventive/anticancer effects. However, the role of B in metabolic rewiring, epigenomic reprogramming, transcriptomic network, NRF2 signaling, and eliciting cancer-preventive effects in colorectal cancer (CRC) HCT116 cell remains unclear. Sodium butyrate (NaB) dose-dependently inhibits the growth of CRC HCT116 cells. NaB inhibits NRF2/NRF2-target genes and blocks NRF2-ARE signaling. NaB increases NRF2 negative regulator KEAP1 expression through inhibiting its promoter methylation. Associative analysis of DEGs (differentially expressed genes) from RNA-seq and DMRs (differentially methylated regions) from CpG methyl-seq identified the tumor suppressor gene ABCA1 and tumor promote gene EGR3 are correlated with their promoters' CpG methylation indicating NaB regulates cancer markers through modulating their promoter methylation. NaB activated the mitochondrial tricarboxylic acid (TCA) cycle while inhibited the methionine metabolism which are both tightly coupled to the epigenetic machinery. NaB regulates the epigenetic enzymes/genes including DNMT1, HAT1, KDM1A, KDM1B, and TET1. Altogether, B's regulation of metabolites coupled to the epigenetic enzymes illustrates the potential underlying biological connectivity between metabolomics and epigenomics. B regulates KEAP1/NRF2 signaling, drives metabolic rewiring, CpG methylomic, and transcriptomic reprogramming contributing to the overall cancer-prevention/anticancer effect in the CRC cell model.

Identifiants

pubmed: 35429118
doi: 10.1002/mnfr.202200028
pmc: PMC9233026
mid: NIHMS1800669
doi:

Substances chimiques

Kelch-Like ECH-Associated Protein 1 0
NF-E2-Related Factor 2 0
Proto-Oncogene Proteins 0
Butyric Acid 107-92-6
Mixed Function Oxygenases EC 1.-
TET1 protein, human EC 1.-
Histone Demethylases EC 1.14.11.-
KDM1A protein, human EC 1.5.-

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2200028

Subventions

Organisme : NIEHS NIH HHS
ID : P30 ES005022
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01 AT009152
Pays : United States

Informations de copyright

© 2022 Wiley-VCH GmbH.

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Auteurs

Lujing Wang (L)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08854, USA.

Ahmad Abdel Fat Shannar (AAF)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08854, USA.

Renyi Wu (R)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.

Pochung Chou (P)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08854, USA.

Md Shahid Sarwar (MS)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.

Hsiao-Chen Kuo (HC)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08854, USA.

Rebecca Mary Peter (RM)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Graduate Program of Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08854, USA.

Yujue Wang (Y)

Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.

Xiaoyang Su (X)

Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.
Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.

Ah-Ng Kong (AN)

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.

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Classifications MeSH