DcR3, stabilized by the RNA-binding protein IGF2BP2, promotes proliferation, invasion, and migration of trophoblast cells and facilitates angiogenesis.

BACKGROUND

Preeclampsia, a pregnancy-related disorder, has high morbidity and mortality rates. Decoy receptor 3 (DcR3) plays a critical role in immune modulation during pregnancy. This study investigated the functional role of DcR3 in trophoblast cell phenotypes.

METHODS

Expression analyses were performed by real-time quantitative polymerase chain reaction and western blot. The influence on HTR-8/Svneo trophoblast cells was evaluated by measuring cell proliferation, migration, invasion, and tube formation. RNA immunoprecipitation and mRNA stability assays were used to confirm the relationship between IGF2BP2 and DcR3 mRNA.

RESULTS

DcR3 overexpression promoted the proliferation (1.34-fold), invasion (1.5-fold), migration (1.16-fold), and tube formation ability (1.3-fold) in HTR-8/Svneo cells, while DcR3 knockdown exhibited opposite effects on these cell phenotypes. DcR3 overexpression also enhanced the tube formation of human umbilical vein endothelial cells (HUVECs, 1.64-fold). Mechanistically, insulin-like growth factor 2 binding protein 2 (IGF2BP2) could bind to DcR3 mRNA and enhanced the stabilization and expression of this transcript. Moreover, the inhibitory effects of IGF2BP2 knockdown on the proliferation (35.2%), invasion (72%), and tube formation (36.4%) of HTR-8/Svneo cells were countervailed by DcR3 overexpression.

CONCLUSION

Collectively, our study suggests that IGF2BP2-stabilized DcR3 promotes the proliferation, migration, invasion, and tube formation of trophoblast cells.