RT Journal Article
SR Electronic
T1 BRD4-Regulated Molecular Targets in Mantle Cell Lymphoma: Insights into Targeted Therapeutic Approach
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 77
OP 89
DO 10.21873/cgp.20169
VO 17
IS 1
A1 TAKU TSUKAMOTO
A1 SHINGO NAKAHATA
A1 RYUICHI SATO
A1 AKINORI KANAI
A1 MASAKAZU NAKANO
A1 YOSHIAKI CHINEN
A1 SAORI MAEGAWA-MATSUI
A1 YAYOI MATSUMURA-KIMOTO
A1 TOMOKO TAKIMOTO-SHIMOMURA
A1 YOSHIMI MIZUNO
A1 SAEKO KUWAHARA-OTA
A1 YUKA KAWAJI
A1 MASAFUMI TANIWAKI
A1 TOSHIYA INABA
A1 KEI TASHIRO
A1 KAZUHIRO MORISHITA
A1 JUNYA KURODA
YR 2020
UL http://cgp.iiarjournals.org/content/17/1/77.abstract
AB 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.