KIF18b-dependent hypomethylation of PARPBP gene promoter enhances oxaliplatin resistance in colorectal cancer.
Exp Cell Res
; 407(2): 112827, 2021 10 15.
Article
en En
| MEDLINE
| ID: mdl-34508743
ABSTRACT
As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Regulación Neoplásica de la Expresión Génica
/
Cinesinas
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Resistencia a Antineoplásicos
/
Metilación de ADN
/
Proteínas de Unión al ADN
/
Oxaliplatino
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Exp Cell Res
Año:
2021
Tipo del documento:
Article