Simultaneous silencing Aurora-A and UHRF1 inhibits colorectal cancer cell growth through regulating expression of DNMT1 and STAT1.
Int J Med Sci
; 18(15): 3437-3451, 2021.
Article
en En
| MEDLINE
| ID: mdl-34522170
ABSTRACT
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 STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Silenciador del Gen
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Proteínas Potenciadoras de Unión a CCAAT
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Ubiquitina-Proteína Ligasas
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Aurora Quinasa A
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Med Sci
Asunto de la revista:
MEDICINA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China