NF-κB and STAT3 co-operation enhances high glucose induced aggressiveness of cholangiocarcinoma cells.
Biliary tract cancer
Cholangiocarcinoma
Diabetes mellitus
High glucose
Interleukin-1β
Nuclear factor-κB
STAT3
Transcriptomics
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
27
06
2020
revised:
17
09
2020
accepted:
28
09
2020
pubmed:
11
10
2020
medline:
15
12
2020
entrez:
10
10
2020
Statut:
ppublish
Résumé
The present report aimed to investigate the underlying genes and pathways of high glucose driving cholangiocarcinoma (CCA) aggressiveness. We screened and compared the gene expression profiles obtained by RNA sequencing, of CCA cells cultured in high and normal glucose. Results from the transcriptomic analysis were confirmed in additional cell lines using in vitro migration-invasion assay, Western blotting and immunocytofluorescence. Data indicated that high glucose increased the expression of interleukin-1β (IL-1β), an upstream regulator of nuclear factor-κB (NF-κB) pathway, through the nuclear localization of NF-κB. High glucose-induced NF-κB increased the migration and invasion of CCA cells and the expression of downstream NF-κB targeted genes associated with aggressiveness, including interleukin-6, a potent triggering signal of the signal transducer and activator of transcription 3 (STAT3) pathway. Such effects were reversed by inhibiting NF-κB nuclear translocation which additionally reduced the phosphorylation of STAT3 at Y705. These results indicate that NF-κB is activated by high glucose and they suggest that NF-κB interaction with STAT3 enhances CCA aggressiveness. Therefore, targeting multiple pathways such as STAT3 and NF-κB might improve CCA treatment outcome especially in condition such as hyperglycemia.
Identifiants
pubmed: 33038372
pii: S0024-3205(20)31301-1
doi: 10.1016/j.lfs.2020.118548
pmc: PMC7686287
mid: NIHMS1636922
pii:
doi:
Substances chimiques
Interleukin-1beta
0
NF-kappa B
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
118548Subventions
Organisme : NHGRI NIH HHS
ID : U54 HG003273
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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