Affiliation:
1. Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2. Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background:
As epigenetic readers, Bromodomain and extraterminal domain (BET) proteins have attracted
immense interest in developing novel therapies targeting this family to inhibit cancer progression. Although the impact
of BRD4 in the carcinogenesis of various tumors has been widely investigated, little is known about the potential roles
of the BET family in gastric cancer.
Methods:
In this cohort study, we have screened the expression profile of the BET protein family, including three
members, BRD2, BRD3 and BRD4, in fresh gastric cancer (GC), adjacent non-tumor and normal gastric tissues, as
well as the anti-cancer effects and molecular mechanisms of BET inhibition in GC cell lines.
Results:
Among GC patients, BRD2, BRD3 and BRD4 showed overexpression, 48.07% (25/52), 61.5% (32/52) and
63.46% (33/52), respectively. The overexpression of BRD3 and BRD4 were remarkably associated with unfavorable
outcomes (HR = 2.023, P = 0.038; HR = 3.874, P = 0.001, respectively). However, multivariate Cox regression analysis
indicated that BRDs mRNA expression could not be used as an independent prognostic factor for GC patients after
adjustment with other variables. I-BET151, a potent pan-inhibitor, suppressing the BET family, decreased cell growth,
migration and invasion of GC cells. Interestingly, I-BET151 induced G1 cell cycle arrest through down-regulation of
c-Myc and its target, CDK2/Cyclin D1 complex.
Conclusions:
Our data provide insights into the prognostic role of the BET family in GC and proposed BET inhibition
as a therapeutic strategy for GC patients.
Funder
National Institute for Medical Research Development (NIMAD), Tehran, Iran
Tehran University of Medical Sciences and Health Services, Tehran, Iran
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
1 articles.
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