Endogenous and exogenous miR-520c-3p modulates CD44-mediated extravillous trophoblast invasion.
Adequate extravillous trophoblast (EVT) invasion is essential for successful placentation. Although miR-520c-3p plays an important role in CD44-mediated invasion in cancer cells, there is little information on whether miR-520c-3p is involved in the regulatory mechanisms of CD44-mediated EVT invasion.



We screened first trimester trophoblast cells and trophoblast cell lines for expression of miR-520c-3p using real-time polymerase chain reaction. The cell invasion assay was performed using EVT cell lines, HTR8/SVneo and HChEpC1b, to investigate the capability of suppressing EVT invasion by miR-520c-3p. Laser microdissection analysis was then used to determine whether miR-520c-3p was present in the first trimester decidua. Finally, the possibility of chorionic villous trophoblast (CVT)-EVT communication via exosomal miR-520c-3p was determined using an in vitro model based on BeWo exosomes and the EVT cell lines as recipient cells.



The miR-520c-3p level was significantly downregulated in EVT cell lines and EVTs. Cell invasion was significantly inhibited in miR-520c-3p-overexpressing cell lines, involving a significant reduction of CD44. Laser microdissection analysis showed that miR-520c-3p in the periarterial area of the decidua was significantly higher than that in the non-periarterial area. Using an in vitro model system, BeWo exosomal miR-520c-3p was internalized into the EVT cells with subsequently reduced cell invasion via CD44 repression.



EVT invasion is synergistically enhanced by the reciprocal expression of endogenous miR-520c-3p and CD44. The present study supports a novel model involving a placenta-associated miRNA function in cell-cell communication in which CVT exosomal miR-520c-3p regulates cell invasion by targeting CD44 in EVTs.
Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan; Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Hironori
H
Takahashi
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Akihide
A
Ohkuchi
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Tomoyuki
T
Kuwata
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Rie
R
Usui
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Yosuke
Y
Baba
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Hirotada
H
Suzuki
Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan.
Tha Thu
TT
Chaw Kyi
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan.
Shigeki
S
Matsubara
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan.
Shigeru
S
Saito
Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan. Electronic address: t-takizawa@nms.ac.jp.
Toshihiro
T
Takizawa
D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C575048:MIRN520 microRNA, human; D035683:MicroRNAs
CD44; Cell invasion; Exosome; Extravillous trophoblast; Human placenta; MicroRNA