Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.
gene regulation
molecular oncology
pancreatic cancer
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
15
11
2017
revised:
06
09
2018
accepted:
12
09
2018
pubmed:
20
10
2018
medline:
28
7
2019
entrez:
20
10
2018
Statut:
ppublish
Résumé
Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis. DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo. We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.
Identifiants
pubmed: 30337373
pii: gutjnl-2017-315690
doi: 10.1136/gutjnl-2017-315690
pmc: PMC6697184
mid: NIHMS1044065
doi:
Substances chimiques
Histone Demethylases
EC 1.14.11.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
1271-1286Subventions
Organisme : NCI NIH HHS
ID : R01 CA136526
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026744
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK041301
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA107486
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027926
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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