Qingqing Zhou, Qi Wang, Yantao Duan, Chi Zhang, Tengfei Liu, Hengrui Liu, Mindi Zhao, Zhihuang Hu
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引用次数: 0
Abstract
BRD9 is involved in multiple physiological and pathological pathways, yet its functional role and molecular mechanisms in gastric cancer (GC) remain largely unexplored. Addressing this knowledge gap is critical given the persistent global mortality burden of GC and the limited efficacy of current therapeutic strategies. BRD9 expression in GC patients was systematically analyzed using immunohistochemical (IHC) assays and transcriptomic datasets. Comprehensive functional validation, employing cellular and murine tumor models, elucidated BRD9’s role in GC progression. Molecular pathways underlying BRD9-mediated gastric carcinogenesis were delineated through integrated approaches, including RNA sequencing, co-immunoprecipitation (co-IP), subcellular fractionation, and luciferase reporter assays. BRD9 was significantly overexpressed in GC and associated with poor patient prognosis. Functionally, BRD9 promoted GC cell proliferation and enhanced DNA damage repair capacity. Mechanistically, elevated BRD9 expression inhibited p53 nuclear translocation via direct binding, subsequently activating the E2F transcription factor family. Notably, we identified that E2F1 directly bound to and transactivated the BRD9 promoter, establishing a positive feedback loop that sustains BRD9 expression. Additionally, BRD9 knockdown sensitized GC cells to cisplatin and oxaliplatin treatment. These findings highlight the critical role of BRD9 in GC progression and its therapeutic potential. The BRD9-p53-E2F1 axis acts as a crucial regulator of GC cell proliferation and DNA damage response. Targeting BRD9 pharmacologically could be a novel therapeutic approach to enhance chemotherapy efficacy and improve treatment outcomes in GC patients.
期刊介绍:
Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer.
The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies.
Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.