ZNF582 promoter methylation predicts cervical cancer radiosensitivity and ZNF582 protein overexpression reduces radiosensitivity by cell cycle arrest in S phase.
Epigenetics
; 17(12): 1786-1799, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-35642528
ABSTRACT
This study aimed to investigate the relationship between ZNF582 promoter methylation (ZNF582m) level and radiosensitivity of cervical cancer and its biological basis. This was a prospective multicenter clinical study, comprising two independent cohorts of locally advanced cervical cancer patients. Exfoliated cervical cells were collected at 0, 24, 30, 36, 48, and 64 Gy to test ZNF582m levels. Radiotherapy response was evaluated according to RECIST Version. RT-PCR and WT were used to detect the mRNA and protein expression levels; MTT and flow cytometry were used to detect the cell viability and cell cycle, respectively. While clone formation and subcutaneous tumorigenesis in nude mice were used to detect the growth of HeLa cells with/without ZNF582 overexpression. In the first cohort, 22 cases achieved complete remission (CR) or partial response (PR), and the other 28 cases exhibited stable disease (SD). Radiotherapy reduced ZNF582m levels among all patients. Initial lever of ZNF582m was significantly higher in the Responder (CR + PR) group than in the SD group. Also, patients with higher initial lever ZNF582m were more sensitive towards radiotherapy than ZNF582m-low patients. The second cohort confirmed the above results. The amplitude of ZNF582m levels were related to the radiotherapeutic response; some patients of ZNF582m-low showed a transient increase in ZNF582m, and present greater radiosensitivity than other ZNF582m-low patients. In vitro, ZNF582 protein overexpression promoted cell cycle arrest in S phase. These results suggested that higher ZNF582m levels predicted greater radiosensitivity in clinical cervical cancer cases. Overexpressed ZNF582 conferred radioresistance by cell cycle arrest in vitro.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Cuello Uterino
Tipo de estudio:
Clinical_trials
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Epigenetics
Asunto de la revista:
GENETICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China