Overexpression of trophoblastic stem cell transcription factor,forkhead boxD3,contributes to malignancy of human choriocarcinoma JAR cells / 中国组织工程研究

ABSTRACT

BACKGROUND: Choriocarcinoma is a kind of trophoblastic neoplasm with highly aggressive phenotypes. Forkhead box D3 (FoxD3) is an embryonic and trophoblastic stem cel 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 cel 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 cel proliferation was evaluatedin vitro by cel counting assay andin vivo by tumor growth. The migration/invasion was determined by transwel 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/invasionin vitro, and suppress thetumor growth with decreased β-human chorionic gonadotropin secretionin 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.