PMID- 30362154
OWN - NLM
STAT- MEDLINE
DCOM- 20200624
LR  - 20200624
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 4
DP  - 2019 Apr
TI  - P2X4R silence suppresses glioma cell growth through BDNF/TrkB/ATF4 signaling 
      pathway.
PG  - 6322-6329
LID - 10.1002/jcb.27919 [doi]
AB  - Purinergic receptor P2X 4 (P2X4R), a member of purinergic channels family and a 
      subtype of ionotropic adenosine triphosphate receptors, plays a critical role in 
      tumorigenesis. Evidence suggested that P2X4R is expressed in rat C6 glioma model, 
      however, its role and the underlying mechanism of action are still unclear in 
      human glioblastoma multiforme (GBM). In the current study, our aim is to examine 
      the function and the molecular basis of P2X4R in GBM. We first observed that GBM 
      cells, U251, T98, U87, U373, and A172 were all high expressed P2X4R, when 
      compared with the normal human astrocytes (NHA) cells. To gain the function of 
      P2X4R, P2X4R silence cells were constructed by transfection with P2X4R small 
      interfering RNA (siRNA). We found that P2X4R deletion impeded T98 and U87 cell 
      viability and proliferation, and further studies indicated that cell apoptosis 
      and caspase-3 activity was increased in T98 and U87 cell transfected with P2X4R 
      siRNA. Subsequently, we confirmed that P2X4R silence suppressed brain-derived 
      neurotrophic factor (BDNF), Trk receptor tyrosine kinases (TrkB), and activating 
      transcription factor 4 (ATF4) expression in T98 and U87 cells. And P2X4R 
      siRNA-induced ATF4-expression inhibition dependent on BDNF/TrkB signaling 
      pathway. The impact of P2X4R silence on T98 and U87 cell growth and apoptosis was 
      reversed by ATF4 overexpression. In summary, this study provides the first 
      evidence that P2X4R plays important roles in GBM cell growth and apoptosis.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Huo, Jun-Feng
AU  - Huo JF
AUID- ORCID: 0000-0001-6460-3570
AD  - Second Ward, Department of Neurosurgery, Huaihe Hospital of Henan University, 
      Kaifeng, China.
FAU - Chen, Xiao-Bing
AU  - Chen XB
AD  - Second Ward, Department of Neurosurgery, Huaihe Hospital of Henan University, 
      Kaifeng, China.
LA  - eng
PT  - Journal Article
DEP - 20181025
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (ATF4 protein, human)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (P2RX4 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Purinergic P2X4)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Activating Transcription Factor 4/metabolism
MH  - Brain Neoplasms/genetics/*metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Glioblastoma/genetics/*metabolism
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - RNA, Small Interfering/*pharmacology
MH  - Receptor, trkB/metabolism
MH  - Receptors, Purinergic P2X4/*genetics/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - P2X4R
OT  - TrkB
OT  - activating transcription factor 4
OT  - brain-derived neurotrophic factor
OT  - glioblastoma multiforme
EDAT- 2018/10/27 06:00
MHDA- 2020/06/25 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/08/09 00:00 [received]
PHST- 2018/09/27 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2020/06/25 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - 10.1002/jcb.27919 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Apr;120(4):6322-6329. doi: 10.1002/jcb.27919. Epub 2018 Oct 
      25.