Overexpression of trophoblastic stem cell transcription factor, forkhead box D3, contributes to malignancy of human choriocarcinoma JAR cells

doi:10.3969/j.issn.2095-4344.2016.10.006

Chinese Journal of Tissue Engineering Research ›› 2016, Vol. 20 ›› Issue (10): 1409-1418.doi: 10.3969/j.issn.2095-4344.2016.10.006

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Overexpression of trophoblastic stem cell transcription factor, forkhead box D3, contributes to malignancy of human choriocarcinoma JAR cells

Liu Yuan¹, Wang Ya-xin¹, Wu Wei-bin¹, Wang Yu-dong², Zhang Hui-juan¹

1 Department of Pathology and Bio-Bank, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

2 Department of Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, China

Received:2015-12-24 Online:2016-03-04 Published:2016-03-04
Contact: Zhang Hui-juan, M.D., Chief physician, Department of Pathology and Bio-Bank, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
About author:Liu Yuan, Master, Physician, Department of Pathology and Bio-Bank, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China Wang Ya-xin, Master, Department of Pathology and Bio-Bank, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China Liu Yuan and Wang Ya-xin contributed equally to this work.
Supported by:
the National Natural Science Foundation of China, No. 81072140, 81172477; the Medical Engineering Interdisciplinary Project of Shanghai Jiao Tong University, No. YG2013MS67, YG2014QN11

Abstract

Abstract:

BACKGROUND: Choriocarcinoma is a kind of trophoblastic neoplasm with highly aggressive phenotypes. Forkhead box D3 (FoxD3) is an embryonic and trophoblastic stem cell transcription factor. It plays important roles in different physical and pathological situations such as embryogenesis, carcinogenesis and tumor progression.

OBJECTIVE: To investigate the role of FoxD3 in choriocarcinoma malignancy and the possible mechanism.

METHODS: The human choriocarcinoma JAR cell line was employed in this study. The mRNA and protein expressions of genes were measured by quantitative RT-PCR (qRT-PCR) and western blot, respectively. The FoxD3 specific short hair RNA was applied to down-regulate gene expression. The cell proliferation was evaluated in vitro by cell counting assay and in vivo by tumor growth. The migration/invasion was determined by transwell assay. The profile of FoxD3 targeted genes was investigated with an Agilent microarray and verified by qRT-PCR.

RESULTS AND CONCLUSION: The FoxD3 mRNA and protein expressions in JAR cells were significantly higher than those in primarily cultured normal trophoblastic cells. Knockdown of FoxD3 by short hair RNA in JAR cells could inhibit cell proliferation and migration/invasion in vitro, and suppress the tumor growth with decreased β-human chorionic gonadotropin secretion in vivo. A profile of seven focal adhesion molecules (ITGA5, ITGB6, THBS4, COL6A3, VTN, NRXN3 and NLGN1) was verified to be targeted by FoxD3. Furthermore, knockdown of FoxD3 by short hair RNA could decrease the activation of focal adhesion kinase. All these findings suggest the overexpression of FoxD3 can contribute to the aggressive phenotype of choriocarcinoma JAR cells by regulating the profile of focal adhesion molecules and focal adhesion kinase.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Liu Yuan, Wang Ya-xin, Wu Wei-bin, Wang Yu-dong, Zhang Hui-juan. Overexpression of trophoblastic stem cell transcription factor, forkhead box D3, contributes to malignancy of human choriocarcinoma JAR cells[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(10): 1409-1418.

Figures/Tables 4

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Overexpression of trophoblastic stem cell transcription factor, forkhead box D3, contributes to malignancy of human choriocarcinoma JAR cells

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