ArticleCancer communications (London, England)2020
BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma.
Article in Cancer communications (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
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- Helicobacter Pylori-induced BRD2 mInternational journal of biological sciences · 2025Article
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- CD7-targeting pro-apoptotic extracellular vesicles: A novel approach for T-cell haematological malignancy therapy.Journal of extracellular vesicles · 2024Article
- Enhancers in T Cell development and malignant lesions.Cell death discovery · 2024Review
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- RGD-p21Ras-scFv expressed prokaryotically on a pilot scale inhibits ras-driven colorectal cancer growth by blocking p21Ras-GTP.BMC cancer · 2024Article
- miR-143 promotes cell proliferation, invasion and migration via directly binding to BRD2 in lens epithelial cells.American journal of translational research · 2024Article
- Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma.Blood science (Baltimore, Md.) · 2023Article
- [The consensus of the diagnosis and treatment of adult T-cell lymphoblastic lymphoma in China (2023)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- The β-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 axis promotes adult T-cell lymphoblastic lymphoma progression and chemoresistance.Journal of experimental & clinical cancer research : CR · 2023Article
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Comprehensive view on genetic features, therapeutic modalities and prognostic models in adult T-cell lymphoblastic lymphoma.Blood science (Baltimore, Md.) · 2022Review
- Identification of novel biomarkers involved in doxorubicin-induced acute and chronic cardiotoxicity, respectively, by integrated bioinformatics.Frontiers in cardiovascular medicine · 2022Article
- The role of protein acetylation in carcinogenesis and targeted drug discovery.Frontiers in endocrinology · 2022Review
- Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.American journal of hematology · 2021Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdult patients with T-cell lymphoblastic lymphoma (T-LBL) are treated with high-intensity chemotherapy regimens, but the response rate is still unsatisfactory because of frequent drug resistance. We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.
methodsGene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues. Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2 (BRD2) and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients. The Ras pull-down assay was performed to monitor Ras activation. Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1 (E2F1)/BRD2 to the RAS guanyl releasing protein 1 (RasGRP1) promoter region. The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.
resultsA total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray. Among them, BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progression-free survival and overall survival of 85 adult T-LBL patients. Furthermore, BRD2 suppressed doxorubicin (Dox)-induced cell apoptosis both in vitro and in vivo. The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2. Besides, OTX015, a bromodomain and extra-terminal (BET) inhibitor, reversed the Dox resistance effect of BRD2. Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.
conclusionsOur data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway. Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with T-LBL.
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