Overexpression of Bromodomain and Extraterminal Domain is Associated with Progression, Metastasis and Unfavorable Outcomes: Highlighting Prognostic and Therapeutic Value of the BET Protein Family in Gastric Cancer.

Autor:	Fard SS; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Kouchaki S; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Salimian Z; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Sotoudeh M; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Mousavi SA; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Alimoghaddam K; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Ghaffari SH; Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2023; Vol. 23 (7), pp. 794-806.
DOI:	10.2174/1871520623666221025145320
Abstrakt:	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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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