JMJD3 promotes the epithelial-mesenchymal transition and migration of glioma cells via the CXCL12/CXCR4 axis

被引：16

作者：

Zou, Shuang ^{[1
]}

Zhang, Dongchen ^{[2
]}

Xu, Zhongwei ^{[1
]}

Wen, Xiaochang ^{[1
]}

Zhang, Yan ^{[1
]}

机构：

[1] Logist Univ Peoples Armed Police Force, Dept Med Serv, Cent Lab, 1 Huizhi Beltway, Tianjin 300309, Peoples R China

[2] First Cent Hosp Baoding, Dept Dermatol, Baoding 071000, Hebei, Peoples R China

来源：

ONCOLOGY LETTERS | 2019年 / 18卷 / 06期

关键词：

Jumonji domain-containing protein 3; C-X-C motif chemokine ligand 12; epithelial-mesenchymal transition; migration; glioma; BREAST-CANCER CELLS; TUMOR-METASTASIS; TARGETED THERAPY; GENE-EXPRESSION; DOWN-REGULATION; RECEPTOR CXCR4; CONTRIBUTES; ACTIVATION; SIGNAL; DEMETHYLASES;

D O I：

10.3892/ol.2019.10972

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：5930 / 5940

页数：11

共 54 条

[1] UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development [J].

Agger, Karl ;

Cloos, Paul A. C. ;

Christensen, Jesper ;

Pasini, Diego ;

Rose, Simon ;

Rappsilber, Juri ;

Issaeva, Irina ;

Canaani, Eli ;

Salcini, Anna Elisabetta ;

Helin, Kristian .

NATURE, 2007, 449 (7163) :731-U10

[2] The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence [J].

Agger, Karl ;

Cloos, Paul A. C. ;

Rudkjaer, Lise ;

Williams, Kristine ;

Andersen, Gitte ;

Christensen, Jesper ;

Helin, Kristian .

GENES & DEVELOPMENT, 2009, 23 (10) :1171-1176

[3] Epithelial-to-mesenchymal transition in FHC-silenced cells: the role of CXCR4/CXCL12 axis [J].

Aversa, I. ;

Zolea, F. ;

Ierano, C. ;

Bulotta, S. ;

Trotta, A. M. ;

Faniello, M. C. ;

De Marco, C. ;

Malanga, D. ;

Biamonte, F. ;

Viglietto, G. ;

Cuda, G. ;

Scala, S. ;

Costanzo, F. .

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2017, 36

[4] Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS [J].

Barradas, Marta ;

Anderton, Emma ;

Acosta, Juan Carlos ;

Li, SiDe ;

Banito, Ana ;

Rodriguez-Niedenfuehr, Marc ;

Maertens, Goedele ;

Banck, Michaela ;

Zhou, Ming-Ming ;

Walsh, Martin J. ;

Peters, Gordon ;

Gil, Jesus .

GENES & DEVELOPMENT, 2009, 23 (10) :1177-1182

[5] The CXCR4 antagonist plerixafor (AMD3100) promotes proliferation of Ewing sarcoma cell lines in vitro and activates receptor tyrosine kinase signaling [J].

Berning, Philipp ;

Schaefer, Christiane ;

Clemens, Dagmar ;

Korsching, Eberhard ;

Dirksen, Uta ;

Potratz, Jenny .

CELL COMMUNICATION AND SIGNALING, 2018, 16

[6] The Intricate Role of CXCR4 in Cancer [J].

Chatterjee, Samit ;

Azad, Babak Behnam ;

Nimmagadda, Sridhar .

EMERGING APPLICATIONS OF MOLECULAR IMAGING TO ONCOLOGY, 2014, 124 :31-82

[7] The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells [J].

Cheng, Yu ;

Song, Yongxi ;

Qu, Jinglei ;

Che, Xiaofang ;

Song, Na ;

Fan, Yibo ;

Wen, Ti ;

Xu, Ling ;

Gong, Jing ;

Wang, Xiaoxun ;

Zhang, Chenlu ;

Qu, Xiujuan ;

Liu, Yunpeng .

TRANSLATIONAL ONCOLOGY, 2018, 11 (02) :487-497

[8] Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease [J].

Cloos, Paul A. C. ;

Christensen, Jesper ;

Agger, Karl ;

Helin, Kristian .

GENES & DEVELOPMENT, 2008, 22 (09) :1115-1140

[9] Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells [J].

Cohen, Evan N. ;

Gao, Hui ;

Anfossi, Simone ;

Mego, Michal ;

Reddy, Neelima G. ;

Debeb, Bisrat ;

Giordano, Antonio ;

Tin, Sanda ;

Wu, Qiong ;

Garza, Raul J. ;

Cristofanilli, Massimo ;

Mani, Sendurai A. ;

Croix, Denise A. ;

Ueno, Naoto T. ;

Woodward, Wendy A. ;

Luthra, Raja ;

Krishnamurthy, Savitri ;

Reuben, James M. .

PLOS ONE, 2015, 10 (07)

[10] Jmjd3 contributes to the control of gene expression in LPS-activated macrophages [J].

De Santa, Francesca ;

Narang, Vipin ;

Yap, Zhei Hwee ;

Tusi, Betsabeh Khoramian ;

Burgold, Thomas ;

Austenaa, Liv ;

Bucci, Gabriele ;

Caganova, Marieta ;

Notarbartolo, Samuele ;

Casola, Stefano ;

Testa, Giuseppe ;

Sung, Wing-Kin ;

Wei, Chia-Lin ;

Natoli, Gioacchino .

EMBO JOURNAL, 2009, 28 (21) :3341-3352

← 1 2 3 4 5 6 →