CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription.
Transl Oncol
; 47: 102038, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38991463
ABSTRACT
BACKGROUND:
Recurrent or metastatic cervical cancer have an extremely low 5-year survival rates about 17% due to limited therapeutic options. CDYL plays a critical role in multiple cancer development, as an oncogene or tumor suppressor in a context-dependent manner. However, the role of CDYL in cervical carcinogenesis has not yet been explored.METHODS:
CDYL expression was examined in cervical cancer and cell lines. The effect of CDYL/IRF2BP2/PD-L1 axis on malignant phenotypes of cervical cancer cells were tested with gain-of-function experiments. A mouse model of cervical cancer was developed to validate the in vitro results.RESULTS:
Clinical data analysis revealed that CDYL was downregulated and associated with a poor prognosis in cervical cancer patients. CDYL overexpression suppressed cervical cancer cells proliferation and invasion in vitro and vivo assays and enhanced the immune response by decreasing PD-L1 expression and reversing the tumor immunosuppressing microenvironment. Mechanistically, CDYL inhibited the PD-L1 expression through transcriptionally suppressing IRF2BP2 in cervical cancer cells.CONCLUSIONS:
Taken together, our findings established the crucial role of CDYL in cervical carcinogenesis and sensitivity for immune checkpoint blockade therapy, and supported the hypothesis that CDYL could be a potential novel immunotherapy response predictive biomarker for cervical cancer patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Transl Oncol
Ano de publicação:
2024
Tipo de documento:
Article