Umemura Kota, Ishioka Shin-Ichi, Endo Toshiaki, Ezaka Yoshiaki, Takahashi Madoka, Saito Tsuyoshi
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
J Obstet Gynaecol Res. 2013 Jan;39(1):67-74. doi: 10.1111/j.1447-0756.2012.01898.x. Epub 2012 Jun 4.
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.
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).
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.
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.
微小RNA-34a（miR-34a）与多种癌症的侵袭和转移相关。胎盘植入的滋养层细胞侵入子宫肌层的方式与癌症侵袭相似。我们研究了miR-34a在胎盘植入发病机制中的作用。
将人绒毛膜癌细胞系JAR作为滋养层细胞模型用于体外实验，将有或无胎盘植入患者手术标本中的胎盘组织用于体内实验。向JAR细胞中加入针对miR-34a的吗啉代反义寡聚核苷酸（miR-34a Morpho/AS），通过实时聚合酶链反应测定miR-34a和纤溶酶原激活物抑制剂-1（PAI-1）的表达。用侵袭实验研究反义寡聚核苷酸、白细胞介素（IL）-6和IL-8在侵袭过程中的作用。通过荧光原位杂交（FISH）研究体内miR-34a的表达。
给予反义寡聚核苷酸后，miR-34a的表达被抑制了65%，加入IL-6和IL-8后miR-34a的表达略有增加。加入IL-6和IL-8后PAI-1的表达降低，给予反义寡聚核苷酸后PAI-1的表达增加。通过抑制miR-34a的表达，侵袭能力增强。在非胎盘植入的滋养层细胞中观察到miR-34a的FISH强表达，在胎盘植入的滋养层细胞中观察到miR-34a的表达明显降低。
胎盘植入中miR-34a的表达下调。体外实验还表明，抑制miR-34a可能通过PAI-1的表达增加JAR细胞的侵袭潜能。
