Journal
TOXICOLOGICAL SCIENCES
Volume 166, Issue 1, Pages 25-38Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfy182
Keywords
BPDE; Human Trophoblast Swan 71 cell; migration and invasion; filopodia formation; PI3K/AKT/CDC42/PAK1 pathway; miR-194-3p
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Funding
- China Key Research and Development Program [2017YFC1002002]
- Fundamental Research Funds for the Central Universities
- National Natural Science Foundation of China [31370793, 81422041]
- Youth 1000 Talent Plan
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Proper migration and invasion of trophoblast cells into endometrium is vital for successful embryo implantation during early pregnancy. Benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) is an ultimate carcinogenic product of benzo[a] pyrene (BaP), which causes multiple trophoblast-related diseases. However, the mechanism of BPDE-inhibited migration/invasion of trophoblast cells is still unclear. In this work, we found that BPDE significantly inhibited the filopodia formation and migration/invasion of human trophoblast Swan 71 cells. BPDE up-regulated the level of miR-194-3p, which further inhibited the phosphoinositide 3-kinase (PI3K)/AKT/cell division cycle 42/p21 (RAC1) activated kinase 1 signaling pathway and depressed the filophdia formation of Swan71 cells. Addition of 740 Y-P, the activator of phosphoinositide 3-kinase, could stimulate cell migration/invasion, confirming the involvement of this pathway. Knock-down of miR-194-3p up-regulated this pathway and promoted filopodia formation and migration/invasion. Conversely, overexpression of miR-194-3p downregulated this pathway and inhibited cell migration/invasion. Therefore, miR-194-3p takes important roles in the BPDEinhibited filopodia formation and cell migration/invasion, providing valuable information in the BPDE-induced dysfunctions of human extravillous trophoblast cells.
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