Simultaneous silencing Aurora-A and UHRF1 inhibits colorectal cancer cell growth through regulating expression of DNMT1 and STAT1.
Animals
Antineoplastic Agents
/ pharmacology
Aurora Kinase A
/ antagonists & inhibitors
Azepines
/ pharmacology
CCAAT-Enhancer-Binding Proteins
/ antagonists & inhibitors
Colorectal Neoplasms
/ drug therapy
CpG Islands
/ drug effects
DNA (Cytosine-5-)-Methyltransferase 1
/ drug effects
DNA Methylation
/ drug effects
Disease Models, Animal
Gene Silencing
/ drug effects
Mice
Promoter Regions, Genetic
Pyrimidines
/ pharmacology
STAT1 Transcription Factor
/ metabolism
Ubiquitin-Protein Ligases
/ antagonists & inhibitors
Aurora-A
STAT1
UHRF1
colorectal cancer cell
Journal
International journal of medical sciences
ISSN: 1449-1907
Titre abrégé: Int J Med Sci
Pays: Australia
ID NLM: 101213954
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
04
2021
accepted:
26
07
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
16
3
2022
Statut:
epublish
Résumé
Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of
Identifiants
pubmed: 34522170
doi: 10.7150/ijms.61969
pii: ijmsv18p3437
pmc: PMC8436113
doi:
Substances chimiques
Antineoplastic Agents
0
Azepines
0
CCAAT-Enhancer-Binding Proteins
0
MLN 8237
0
Pyrimidines
0
STAT1 Transcription Factor
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
Dnmt1 protein, mouse
EC 2.1.1.37
Ubiquitin-Protein Ligases
EC 2.3.2.27
Uhrf1 protein, mouse
EC 2.3.2.27
Aurora Kinase A
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3437-3451Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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