StarD7 Knockdown modulates ABCG2 expression, cell migration and differentiation of human choriocarcinoma JEG3 cells

FLORES MARTIN J; RENA VC; MÁRQUEZ S; PANZETTA DUTARI G; GENTI RAIMONDI S

Buenos Aires

Workshop; Fronteras en Biociencia. Workshop; 2012

IBIOBA and Max Planck

StAR-related lipid transfer domain containing 7 (StarD7) is a member of the START-domain protein family whose function still remains unclear. Our data from an explorative microarray assay performed with mRNAs from StarD7 siRNA-transfected JEG-3 cells indicated that ABCG2 (ATP-binding cassette sub-family G member 2) was one of the most abundantly downregulated mRNAs.  Here, we have confirmed that knocking down StarD7 mRNA lead to a decrease in the xenobiotic/ lipid transporter ABCG2 at both the mRNA and protein levels. Also a concomitant reduction in phospholipid synthesis was detected. Wound healing and transwell assays revealed that JEG-3 cell migration was significantly diminished. Conversely, biochemical differentiation markers such as human chorionic gonadotrophin β-subunit (βhCG) protein synthesis and secretion as well as βhCG and syncytin-1 mRNAs were increased. In addition, desmoplakin immunostaining suggested that there was a reduction of intercellular desmosomes between adjacent JEG-3 cells after knocking down StarD7.   Altogether these findings provide evidence for a new role for StarD7 in cell physiology indicating that StarD7 reduction modulates ABCG2 multidrug transporter level, cell migration and biochemical and morphological differentiation marker expression in a human trophoblast cell model. Supported by CONICET, FONCyT, MinCyT of Córdoba and SECyT-UNC