Promoter Hypermethylation Promotes the Binding of Transcription Factor NFATc1, Triggering Oncogenic Gene Activation in Pancreatic Cancer.
gene regulation
pancreatic ductal adenocarcinoma
promoter methylation
transcription factors
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
11 Sep 2021
11 Sep 2021
Historique:
received:
08
04
2021
revised:
14
05
2021
accepted:
08
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
29
9
2021
Statut:
epublish
Résumé
Studies have indicated that some genes involved in carcinogenesis are highly methylated in their promoter regions but nevertheless strongly transcribed. It has been proposed that transcription factors could bind specifically to methylated promoters and trigger transcription. We looked at this rather comprehensively for pancreatic ductal adenocarcinoma (PDAC) and studied some cases in more detail. Some 2% of regulated genes in PDAC exhibited higher transcription coupled to promoter hypermethylation in comparison to healthy tissue. Screening 661 transcription factors, several were found to bind specifically to methylated promoters, in particular molecules of the NFAT family. One of them-NFATc1-was substantially more strongly expressed in PDAC than control tissue and exhibited a strong oncogenic role. Functional studies combined with computational analyses allowed determining affected genes. A prominent one was gene
Identifiants
pubmed: 34572796
pii: cancers13184569
doi: 10.3390/cancers13184569
pmc: PMC8471171
pii:
doi:
Types de publication
Journal Article
Langues
eng
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