Overexpression of BRD4 in Gastric Cancer and its Clinical Significance as a Novel Therapeutic Target

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BACKGROUND: BRD4 is a member of the bromodomain and extra terminal domain (BET) family of proteins, containing two bromodomains and one extra terminal domain, and is overexpressed in several human malignancies. However, its expression in gastric cancer has not yet been well illustrated.

OBJECTIVE: This study aimed to elucidate the overexpression of BRD4 in gastric cancer and its clinical significance as a novel therapeutic target.

METHODS: Fresh gastric cancer tissues and paraffin-embedded specimens of gastric cancer patients were collected, and the BRD4 expression was examined by Western Blot Analysis (WB) and Immunohistochemistry Analysis (IHC), respectively. The possible relationship between BRD4 expression and the clinicopathological features as well as survival in gastric cancer patients was analyzed. The effect of BRD4 silencing on human gastric cancer cell lines was investigated by MTT assay, WB, wound healing assay, and Transwell invasion.

RESULTS: The results showed that the expression level in tumor tissues and adjacent tissues was significantly higher than that in normal tissues, respectively (P < 0.01). BRD4 expression level in gastric cancer tissues was strongly correlated with the degree of tumor differentiated degree (P = 0.033), regional lymph nodes metastasis (P = 0.038), clinical staging (P = 0.002), and survival situation (P = 0.000), while the gender (P = 0.564), age (P = 0.926) and infiltrating depth (P = 0.619) of patients were not associated. Increased BRD4 expression resulted in poor overall survival (P = 0.003). In in vitro assays, BRD4 small interfering RNA resulted in significantly decreased BRD4 protein expression, therefore inhibiting proliferation, migration, and invasion of gastric cancer cells.

CONCLUSION: BRD4 might be a novel biomarker for the early diagnosis, prognosis, and therapeutic target in gastric cancer.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Current cancer drug targets - 24(2024), 2 vom: 23., Seite 167-177

Sprache:

Englisch

Beteiligte Personen:

Zhang, Mengying [VerfasserIn]
Huang, Hong [VerfasserIn]
Wei, Meijiao [VerfasserIn]
Sun, Mengjia [VerfasserIn]
Deng, Guojin [VerfasserIn]
Hu, Shuiqing [VerfasserIn]
Wang, Hongbo [VerfasserIn]
Gong, Yanling [VerfasserIn]

Links:

Volltext

Themen:

BRD4
BRD4 protein, human
Bromodomain Containing Proteins
Cell Cycle Proteins
Gastric cancer
Journal Article
Nuclear Proteins
Prognosis
Proliferation
SiRNA
Transcription Factors
Western blot

Anmerkungen:

Date Completed 31.01.2024

Date Revised 31.01.2024

published: Print

Citation Status MEDLINE

doi:

10.2174/1568009623666230606164030

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM357845129