Loss of selenocysteine insertion sequence binding protein 2 suppresses the proliferation, migration/invasion and hormone secretion of human trophoblast cells via the PI3K/Akt and ERK signaling pathway
- PMID: 28623977
- DOI: 10.1016/j.placenta.2017.05.007
Loss of selenocysteine insertion sequence binding protein 2 suppresses the proliferation, migration/invasion and hormone secretion of human trophoblast cells via the PI3K/Akt and ERK signaling pathway
Abstract
Introduction: Selenocysteine insertion binding protein 2 (SECISBP2) plays a vital role in selenocysteine incorporation into selenoprotein in many creatures. However, the impact of SECISBP2 in development of trophoblast cells remains unclear. The aim of this study was to investigate the roles of SECISBP2 in human trophoblast cells and the underlying molecular mechanism.
Methods: Low-expression of SECISBP2 in trophoblast cells was achieved by transfection with siRNAs. Then protein levels of selenoproteins and MDA content were performed to evaluate the levels of oxidative stress. CCK-8 assays, transwell chamber assay and wound healing assay were used to assess the trophoblast proliferation, migration/invasion. Production of β-hCG and progesterone was quantified to estimate the effect of SECISBP2 on hormone secretion. The underlying mechanisms were also examined in two trophoblast cell lines.
Results: Knockdown of SECISBP2 clearly reduced the levels of some selenoproteins, including GPx1, SelK, Dio2 (p < 0.05). On the contrary, the levels of oxidative stress presented as MDA content markedly increased in two cell lines (p < 0.05). In addition, proliferative, migratory and invasive abilities of trophoblast cells were significantly suppressed when SECISBP2 was partially deleted (p < 0.05). Furthermore, silencing SECISBP2 reduced the expression of β-hCG at mRNA and protein levels (p < 0.05), and inhibited the production of progesterone (p < 0.01). The PI3K/Akt and ERK signaling pathway were found to involve in the progress (p < 0.05).
Discussion: Our results suggest that the decreased SECISBP2 impaired trophoblast proliferation, migration/invasion and hormone secretion through inactivation of the PI3K/Akt and ERK signaling pathway may provide an insight into the preeclampsia and miscarriage induced by selenium deficiency.
Keywords: Hormone secretion; Migration/invasion; Proliferation; SECISBP2; Trophoblast.
Copyright © 2017. Published by Elsevier Ltd.
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