PMID- 31788067
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 18
IP  - 6
DP  - 2019 Dec
TI  - JMJD3 promotes the epithelial-mesenchymal transition and migration of glioma 
      cells via the CXCL12/CXCR4 axis.
PG  - 5930-5940
LID - 10.3892/ol.2019.10972 [doi]
AB  - Histone H3K27 demethylase Jumonji domain-containing protein 3 (JMJD3) is involved 
      in somatic cell differentiation and tumor progression; however, the underlying 
      mechanisms of JMJD3 in cancer progression are yet to be fully explored. To 
      improve understanding regarding the function of JMJD3 in brain tumor cells, the 
      present study investigated the effects of JMJD3 on the epithelial-mesenchymal 
      transition (EMT) and migration in glioma cells, and the underlying mechanisms 
      involving the C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine 
      receptor 4 (CXCR4) axis. Immunohistochemical staining of a tissue microarray of 
      glioma samples confirmed that JMJD3 overexpression could stratify highly 
      metastatic glioma. The overexpression of JMJD3 induced a spindle-shaped 
      morphology, promoted N-cadherin expression, inhibited E-cadherin expression and 
      enhanced the migration ability of U-251MG and U-87MG American Type Culture 
      Collection cells. The expression of E-cadherin and N-cadherin were assessed by 
      western blotting and reverse transcription-quantitative polymerase chain 
      reaction, and cell migration was evaluated using a Transwell migration assay and 
      wound-healing. The overexpression of JMJD3 upregulated CXCL12 expression in a 
      demethylase activity-dependent manner as ChIP assays revealed a decrease in H3K27 
      trimethylation at the CXCL12 promoter following overexpression of JMJD3 in U-87MG 
      ATCC cells. Accordingly, CXCL12 overexpression was sufficient to rescue the 
      suppressive effects of JMJD3 inhibition on the EMT and migration in glioma cells. 
      In addition, CXCR4 expression was not regulated by JMJD3, but the interruption of 
      CXCR4 caused by the CXCR4 inhibitor AMD3100 abolished the promotional effect of 
      JMJD3 on EMT and migration in glioma cells. Collectively, these results suggested 
      that JMJD3 promoted EMT and migration in glioma cells via the CXCL12/CXCR4 axis. 
      The present study described a novel epigenetic mechanism regulating tumor cell 
      EMT and migration, and provided a novel direction for glioma diagnosis and 
      treatment.
CI  - Copyright: (c) Zou et al.
FAU - Zou, Shuang
AU  - Zou S
AD  - Central Laboratory, Department of Medical Service, Logistics University of 
      People's Armed Police Force, Tianjin 300309, P.R. China.
FAU - Zhang, Dongchen
AU  - Zhang D
AD  - Department of Dermatology, The First Central Hospital of Baoding, Baoding, Hebei 
      071000, P.R. China.
FAU - Xu, Zhongwei
AU  - Xu Z
AD  - Central Laboratory, Department of Medical Service, Logistics University of 
      People's Armed Police Force, Tianjin 300309, P.R. China.
FAU - Wen, Xiaochang
AU  - Wen X
AD  - Central Laboratory, Department of Medical Service, Logistics University of 
      People's Armed Police Force, Tianjin 300309, P.R. China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Central Laboratory, Department of Medical Service, Logistics University of 
      People's Armed Police Force, Tianjin 300309, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20191009
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC6865580
OTO - NOTNLM
OT  - C-X-C motif chemokine ligand 12
OT  - Jumonji domain-containing protein 3
OT  - epithelial-mesenchymal transition
OT  - glioma
OT  - migration
EDAT- 2019/12/04 06:00
MHDA- 2019/12/04 06:01
PMCR- 2019/10/09
CRDT- 2019/12/03 06:00
PHST- 2018/11/15 00:00 [received]
PHST- 2019/06/20 00:00 [accepted]
PHST- 2019/12/03 06:00 [entrez]
PHST- 2019/12/04 06:00 [pubmed]
PHST- 2019/12/04 06:01 [medline]
PHST- 2019/10/09 00:00 [pmc-release]
AID - OL-0-0-10972 [pii]
AID - 10.3892/ol.2019.10972 [doi]
PST - ppublish
SO  - Oncol Lett. 2019 Dec;18(6):5930-5940. doi: 10.3892/ol.2019.10972. Epub 2019 Oct 
      9.