Cancer genomics & proteomics · 2020
BRD4-Regulated Molecular Targets in Mantle Cell Lymphoma: Insights into Targeted Therapeutic Approach.
СтатьяНазвание и аннотация: Перевод в очереди
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Tsukamoto Taku, Nakahata Shingo, Sato Ryuichi, Kanai Akinori, Nakano Masakazu, Chinen Yoshiaki, Maegawa-Matsui Saori, Matsumura-Kimoto Yayoi, Takimoto-Shimomura Tomoko, Mizuno Yoshimi, Kuwahara-Ota Saeko, Kawaji Yuka, Taniwaki Masafumi, Inaba Toshiya, Tashiro Kei, Morishita Kazuhiro, Kuroda Junya
Аннотация
BACKGROUND: Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma.
MATERIALS AND METHODS: In order to uncover direct BRD4-regulated targets in MCL, we performed integrated analysis using the pathway database and the results of both gene-expression profiling and chromatin immunoprecipitation with parallel sequencing for BRD4.
RESULTS: Treatment with BRD4 inhibitor I-BET151 exerted a dose-dependent inhibitory effect on cell proliferation in MCL cell lines. BRD4 was found to directly regulate series of genes involved in the B-cell receptor (BCR) signaling pathway, including B-cell linker (BLNK), paired box 5 (PAX5), and IKAROS family zinc finger 3 (IKZF3), and several oncogenes, such as MYB. Indeed, the combinatory inhibition of BCR pathway and IKZF showed an additive antitumor effect.
CONCLUSION: Concomitant targeting multiple BRD4-regulated molecules may constitute a rational therapeutic strategy for MCL.
MATERIALS AND METHODS: In order to uncover direct BRD4-regulated targets in MCL, we performed integrated analysis using the pathway database and the results of both gene-expression profiling and chromatin immunoprecipitation with parallel sequencing for BRD4.
RESULTS: Treatment with BRD4 inhibitor I-BET151 exerted a dose-dependent inhibitory effect on cell proliferation in MCL cell lines. BRD4 was found to directly regulate series of genes involved in the B-cell receptor (BCR) signaling pathway, including B-cell linker (BLNK), paired box 5 (PAX5), and IKAROS family zinc finger 3 (IKZF3), and several oncogenes, such as MYB. Indeed, the combinatory inhibition of BCR pathway and IKZF showed an additive antitumor effect.
CONCLUSION: Concomitant targeting multiple BRD4-regulated molecules may constitute a rational therapeutic strategy for MCL.
Предметные рубрики MeSH
ApoptosisBiomarkers, TumorCell Cycle ProteinsCell ProliferationGene Expression Regulation, NeoplasticHeterocyclic Compounds, 4 or More RingsHumansLymphoma, Mantle-CellMolecular Targeted TherapyProtein Interaction Domains and MotifsTranscription FactorsTumor Cells, CulturedBromodomain Containing Proteins