MicroRNAs (miRNAs) are emerging as important regulators in the pathogenesis of pre-eclampsia (PE). Recent evidence has reported that miR-454 plays an important role in regulating cell proliferation and invasion. The decreased proliferation and invasion of trophoblast cells contribute to the pathogenesis of PE. However, whether miR-454 is involved in the regulation of trophoblast cell proliferation and invasion remains unknown. In this study, we aimed to investigate the potential role and underlying mechanism of miR-454 in regulating trophoblast cell proliferation and invasion in vitro. We found that miR-454 expression was significantly decreased in placental tissues from PE patients compared to controls. Transfection of miR-454 mimics promoted the proliferation, reduced the apoptosis, and increased invasion of trophoblast cells, while transfection of miR-454 inhibitor showed opposite effects. Bioinformatics analysis showed that activin receptor-like kinase 7 (ALK7) was a potential target gene of miR-454. Dual-luciferase reporter assay showed miR-454 directly targeted the 3′-untranslated region of AKL7. Further experiments showed that miR-454 negatively regulated ALK7 expression. Interestingly, transfection of miR-454 mimics significantly abrogated the inhibitory effect of Nodal on trophoblast cell proliferation and invasion. Moreover, overexpression of ALK7 markedly reversed the promotion effect of miR-454 on trophoblast cell proliferation and invasion. Overall, our results suggest that miR-454 promotes the proliferation and invasion of trophoblast cells by downregulation of ALK7. Our study suggests that miR-454 may play critical roles in the pathogenesis of PE and serve as a potential therapeutic target for treatment of PE.

微小RNA（miRNA）在子痫前期（PE）的发病机理中正成为重要的调节剂。最近的证据报道，miR-454在调节细胞增殖和侵袭中起重要作用。滋养层细胞增殖和侵袭的减少与PE的发病机理有关。然而，miR-454是否参与滋养层细胞增殖和侵袭的调控仍是未知的。在这项研究中，我们旨在研究miR-454在调节体外滋养层细胞增殖和侵袭中的潜在作用及其潜在机制。我们发现，与对照组相比，PE患者胎盘组织中的miR-454表达显着降低。miR-454模拟物的转染促进了滋养层细胞的增殖，减少了细胞凋亡并增加了侵袭性，而转染miR-454抑制剂则显示相反的效果。生物信息学分析表明，激活素受体样激酶7（ALK7）是miR-454的潜在靶基因。双荧光素酶报告基因测定显示miR-454直接靶向AKL7的3'-非翻译区。进一步的实验表明，miR-454负调控ALK7表达。有趣的是，miR-454模拟物的转染显着消除了Nodal对滋养层细胞增殖和侵袭的抑制作用。此外，ALK7的过表达显着逆转了miR-454对滋养层细胞增殖和侵袭的促进作用。总的来说，我们的结果表明miR-454通过下调ALK7促进滋养细胞的增殖和侵袭。