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Roles of microRNA‐34a in the pathogenesis of placenta accreta
Author(s) -
Umemura Kota,
Ishioka Shinichi,
Endo Toshiaki,
Ezaka Yoshiaki,
Takahashi Madoka,
Saito Tsuyoshi
Publication year - 2013
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/j.1447-0756.2012.01898.x
Subject(s) - placenta accreta , trophoblast , medicine , pathogenesis , in vivo , placenta , andrology , metastasis , in situ hybridization , cancer research , microrna , pathology , gene expression , biology , cancer , pregnancy , gene , fetus , genetics , biochemistry , microbiology and biotechnology
Aim: 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 .