PMID- 29568956
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200306
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 52
IP  - 5
DP  - 2018 May
TI  - Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in 
      human glioma U251 cells.
PG  - 1415-1426
LID - 10.3892/ijo.2018.4324 [doi]
AB  - Bromodomain containing 4 (BRD4), a member of the bromodomain and extra-terminal 
      family, has become a promising drug target for numerous types of cancer. BRD4 has 
      been reported to be deregulated in gliomas; however, the precise molecular 
      pathways regulated by BRD4 remained elusive. In the present study, BRD4 
      expression was silenced in the glioma cell line U251 and the results demonstrated 
      that BRD4 knockdown attenuated cell proliferation and promoted cell apoptosis. A 
      genome-wide analysis of BRD4-regulated transcripts in U251 cells was performed 
      using microarray to reveal the possible molecular mechanism. A total of 3,529 
      differentially expressed genes were identified; 1,648 of these genes were 
      upregulated and 1,881 were downregulated. The results of the gene ontology 
      analysis revealed that these genes were mainly involved in membrane organization, 
      mitotic cell cycle, cell division and DNA replication. Pathway analysis revealed 
      that the pathways altered following BRD4 knockdown included multiple cellular 
      processes, such as cell cycle and apoptosis. Candidate genes were identified 
      through global signal transduction network analysis and were validated using 
      reverse transcription-quantitative polymerase chain reaction and western blot 
      analyses. The results demonstrated that BRD4 knockdown decreased the expression 
      of KRAS proto-oncogene GTPase (KRAS). Downregulated KRAS expression in U251 cells 
      restrained cell proliferation and promoted cell apoptosis, suggesting that the 
      effect of BRD4 on glioma cells might occur through the Ras pathway. In 
      conclusion, the present results confirmed the role of BRD4 in glioma and provided 
      information for further exploration of the molecular mechanism of BRD4 in glioma 
      development and progression.
FAU - Du, Zhanhui
AU  - Du Z
AD  - The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health Qilu Hospital, 
      Shandong University, Jinan, Shandong 250012, P.R. China.
FAU - Song, Xiuxiang
AU  - Song X
AD  - Department of Anaesthesiology, The People's Hospital of Jimo City, Qingdao, 
      Shandong 266200, P.R. China.
FAU - Yan, Fangfang
AU  - Yan F
AD  - Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, 
      Jinan, Shandong 250012, P.R. China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Institute of Pathology and Pathophysiology, Shandong University School of 
      Medicine, Jinan, Shandong 250012, P.R. China.
FAU - Zhao, Yuxia
AU  - Zhao Y
AD  - Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, 
      Jinan, Shandong 250012, P.R. China.
FAU - Liu, Shangming
AU  - Liu S
AD  - The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health Qilu Hospital, 
      Shandong University, Jinan, Shandong 250012, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180316
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
SB  - IM
PMC - PMC5873870
EDAT- 2018/03/24 06:00
MHDA- 2018/03/24 06:01
PMCR- 2018/03/16
CRDT- 2018/03/24 06:00
PHST- 2017/09/25 00:00 [received]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2018/03/24 06:01 [medline]
PHST- 2018/03/24 06:00 [entrez]
PHST- 2018/03/16 00:00 [pmc-release]
AID - ijo-52-05-1415 [pii]
AID - 10.3892/ijo.2018.4324 [doi]
PST - ppublish
SO  - Int J Oncol. 2018 May;52(5):1415-1426. doi: 10.3892/ijo.2018.4324. Epub 2018 Mar 
      16.