Aberrant Super-Enhancer Landscape in Enzalutamide-Resistant Prostate Cancer Cells.
Genet Test Mol Biomarkers
; 28(6): 243-256, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38722048
ABSTRACT
Background:
Castration-resistant prostate cancer (CRPC), which has developed resistance to next-generation antiandrogens, such as enzalutamide (Enz), is a lethal disease. Furthermore, transcriptional regulation by super enhancers (SEs) is crucial for the growth and spread of prostate cancer, as well as drug resistance. The functions of SEs, a significant class of noncoding DNA cis-regulatory elements, have been the subject of numerous recent studies in the field of cancer research. Materials andMethods:
The goal of this research was to identify SEs associated with Enz resistance in C4-2B cells using chromatin immunoprecipitation sequencing and cleavage under targets and tagmentation (CUT&Tag). Using HOMER analysis to predict protein/gene-binding motifs, we identified master transcription factors (TFs) that may bind to SE sites. Using small interfering RNA, WST-1 assays, and qRT-PCR, we then confirmed the associations between TFs of SEs and Enz resistance.Results:
A total of 999 SEs were screened from C4-2B EnzR cells in total. Incorporating analysis with RNA-seq data revealed 41 SEs to be strongly associated with the promotion of Enz resistance. In addition, we finally predicted that master TFs bind to SE-binding regions. Subsequently, we selected zinc finger protein 467 (ZFP467) and SMAD family member 3 to confirm the functional connections of master TFs with Enz resistance through SEs (ZNF467).Conclusions:
In this study, SMAD3 and ZNF467 were found to be closely related to Enz-resistant CRPC. Our research uncovered a sizable group of SEs linked to Enz resistance in prostate cancer, dissected the mechanisms underlying SE Enz resistance, and shed light on potential clinical uses for SEs.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Feniltiohidantoína
/
Factores de Transcripción
/
Benzamidas
/
Regulación Neoplásica de la Expresión Génica
/
Elementos de Facilitación Genéticos
/
Resistencia a Antineoplásicos
/
Neoplasias de la Próstata Resistentes a la Castración
/
Nitrilos
Límite:
Humans
/
Male
Idioma:
En
Revista:
Genet Test Mol Biomarkers
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China