PMID- 29937714
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 11
DP  - 2018
TI  - Transcriptional Repression of p53 by PAX3 Contributes to Gliomagenesis and 
      Differentiation of Glioma Stem Cells.
PG  - 187
LID - 10.3389/fnmol.2018.00187 [doi]
LID - 187
AB  - Although there are available therapies as surgery, chemotherapy and radiation, 
      glioblastoma (GBM) still has been considered as the most common and overwhelming 
      primary tumor of brain. In GBM, the brain glioma stem cells (BGSCs) were 
      identified and played a crucial role in resistance of GBM to conventional 
      therapies described above. PAX3 was previously identified by our group as a 
      diagnostic/prognostic marker and a therapeutic regulator in the therapy of GBM. 
      Here, we hypothesized PAX3/p53 axis promoted the process of differentiation, 
      regulating to the cancer stem cell properties, such as proliferation and 
      migration. The correlation between PAX3 and p53 in GBM were first clarified. 
      Immunofluorescence of p53 was shown activated following BGSCs differentiation. We 
      further identified that PAX3 might specifically bind to the promoter of p53 gene, 
      and transcriptionally repressed p53 expression. ChIP assay further confirmed that 
      PAX3/p53 axis regulated the differentiation process of BGSCs. Then, the function 
      of PAX3 in BGSCs were sequentially investigated in vitro and in vivo. Ectopic 
      PAX3 expression promoted BGSCs growth and migration while PAX3 knockdown 
      suppressed BGSCs growth, migration in vitro and in vivo. Similar to PAX3 
      overexpression, p53 inhibition also showed increase in growth and migration of 
      differentiated BGSCs. Regarding the functional interaction between PAX3 and p53, 
      PAX3 knockdown-mediated decrease in proliferation was partially rescued by p53 
      inhibition. Hypoxia significantly promoted the migration potential of BGSCs. In 
      addition, hypoxia inducible factor-1alpha (HIF-1alpha) might be a potential upstream 
      regulator of PAX3 in differentiated BGSCs under hypoxia. Our work may provide a 
      supplementary mechanism in regulation of the BGSCs differentiation and their 
      functions, which should provide novel therapeutic targets for GBM in future.
FAU - Zhu, Hui
AU  - Zhu H
AD  - Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
      Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, 
      Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
FAU - Wang, Hongkui
AU  - Wang H
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, 
      Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
FAU - Huang, Qingfeng
AU  - Huang Q
AD  - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Liu, Qianqian
AU  - Liu Q
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, 
      Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
AD  - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Guo, Yibing
AU  - Guo Y
AD  - Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
      Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
FAU - Lu, Jingjing
AU  - Lu J
AD  - Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
      Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
FAU - Li, Xiaohong
AU  - Li X
AD  - Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
      Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
FAU - Xue, Chengbin
AU  - Xue C
AD  - Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
      Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 
      Nantong, China.
AD  - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, 
      Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
FAU - Han, Qianqian
AU  - Han Q
AD  - National Institute for Food and Drug Control, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20180608
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC6003214
OTO - NOTNLM
OT  - PAX3
OT  - glioma
OT  - p53
OT  - stem cells
OT  - tumor microenvironment
EDAT- 2018/06/26 06:00
MHDA- 2018/06/26 06:01
PMCR- 2018/01/01
CRDT- 2018/06/26 06:00
PHST- 2017/10/03 00:00 [received]
PHST- 2018/05/14 00:00 [accepted]
PHST- 2018/06/26 06:00 [entrez]
PHST- 2018/06/26 06:00 [pubmed]
PHST- 2018/06/26 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2018.00187 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2018 Jun 8;11:187. doi: 10.3389/fnmol.2018.00187. eCollection 
      2018.