Roles of microRNA-34a in the pathogenesis of placenta accreta.
OBJECTIVE
MicroRNA-34a (miR-34a) is associated with invasion and metastasis of various cancers. The trophoblastic cells of placenta accreta invade into the myometrium in a similar way to the invasion of cancers. We studied the roles of miR-34a in the pathogenesis of placenta accreta.


METHODS
The human choriocarcinoma cell line JAR was used for in vitro experiments as a model of trophoblasts, and placental tissues from the operative specimen of patients with or without placenta accreta were used for experiments in vivo. Morpholino antisense oligomer against miR-34a (miR-34a Morpho/AS) was added to JAR, and the expression of miR-34a and plasminogen activator inhibitor-1 (PAI-1) was determined by real time PCR. The effects of antisense, interleukin (IL)-6 and IL-8 in the process of invasion were studied with an invasion assay. Expression of miR-34a in vivo was studied with the use of fluorescent in situ hybridization (FISH).


RESULTS
Expression of miR-34a was inhibited by 65% with the administration of antisense, and a slight increase in miR-34a expression was observed with the addition of IL-6 and IL-8. PAI-1 expression decreased with the addition of IL-6 and IL-8, and increased with the administration of antisense. There was an increase in invasive capacity through the inhibition of miR-34a expression. Strong FISH expression of miR-34a was observed in trophoblast cells of non-placenta accreta, and a clear decrease in miR-34a expression was observed in those of placenta accreta.


CONCLUSIONS
Expression of miR-34a was downregulated in placenta accreta. In vitro experiments also showed that the invasive potential of JAR increased by suppressing miR-34a, probably through the expression of PAI-1.
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Kota
K
Umemura
Shin-Ichi
S
Ishioka
Toshiaki
T
Endo
Yoshiaki
Y
Ezaka
Madoka
M
Takahashi
Tsuyoshi
T
Saito
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D010921:Placenta Accreta / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1