New insights into the function of Cullin 3 in trophoblast invasion and migration

Abstract

Cullin 3 (CUL3), a scaffold protein, assembles a large number of ubiquitin ligase complexes, similar to Skp1-Cullin 1-F-box protein complex. Several genetic models have shown that CUL3 is crucial for early embryonic development. Nevertheless, the role of CUL3 in human trophoblast function remains unclear. In this study, immunostaining revealed that CUL3 was strongly expressed in the villous cytotrophoblasts, the trophoblast column, and the invasive extravillous trophoblasts. Silencing CUL3 significantly inhibited the outgrowth of villous explant ex vivo and decreased invasion and migration of trophoblast HTR8/SVneo cells. Furthermore, CUL3 siRNA decreased pro-MMP9 activity and increased the levels of TIMP1 and 2. We also found that the level of CUL3 in the placental villi from pre-eclamptic patients was significantly lower as compared to that from their gestational age-matched controls. Moreover, in the lentiviral-mediated placenta-specific CUL3 knockdown mice, lack of CUL3 resulted in less invasive trophoblast cells in the maternal decidua. Taken together, these results suggest an essential role for CUL3 in the invasion and migration of trophoblast cells, and dysregulation of its expression may be associated with the onset of pre-eclampsia.

Downregulation of Talin-1 expression associates with increased proliferation and migration of vascular smooth muscle cells in aortic dissection

“…They have been confirmed participated in regulating cell’s proliferation [40–42]. Some studies found that Cullin-3 and beta actin regulated cell migration [43, 44]. The relationship between these proteins and Talin-1 has not been researched..…”

Expression of Alpha-Enolase 1 (ENO1) in Villi from Patients with Recurrent Miscarriage and Its Effect on Proliferation and Invasion of Villous Trophoblasts

“…Trophoblast cell dysfunction can lead to pregnancy-related diseases such as intrauterine growth restriction, preeclampsia, eclampsia, spontaneous abortion, premature delivery, and choriocarcinoma [14].…”

Cullin 3 targets methionine adenosyltransferase IIα for ubiquitylation‐mediated degradation and regulates colorectal cancer cell proliferation

“…The discovery that CUL3 controlled the abundance of TIAM1, the activity of RAC1 (the substrate of TIAM1) and the retinoic acid response suggested that CUL3 was implicated in cell differentiation, proliferation, apoptosis and other cellular processes. Recent research demonstrated an essential role for CUL3 in the invasion and migration of trophoblast cells . CUL3 might participate in bladder cancer aggressiveness by modifying the expression of cytoskeleton proteins .…”