Abstract
BackgroundPreeclampsia (PE) is a pregnancy-specific syndrome manifested by on-set of hypertension and proteinuria after 20 weeks of gestation. Abnormal placenta development has been generally accepted as initial cause of the disorder. Recently, miR-195 was found to be down-regulated in preeclamptic placentas compared with normal pregnant ones, indicating possible association of this small molecule with placental pathology of preeclampsia. By far the function of miR-195 in the development of placenta remains unknown.Methodology/Principal FindingsBioinformatic assay predicted ActRIIA as one of the targets for miR-195. By using Real-time PCR, Western blotting and Dual Luciferase Assay, we validated that ActRIIA was the direct target of miR-195 in human trophoblast cells. Transwell insert invasion assay showed that miR-195 could promote cell invasion in trophoblast cell line, HTR8/SVneo cells, and the effect could be abrogated by overexpressed ActRIIA. In preeclamptic placenta tissues, pri-miR-195 and mature miR-195 expressions were down-regulated, whereas ActRIIA level appeared to be increased when compared with that in gestational-week-matched normal placentas.Conclusions/SignificanceThis is the first report on the function of miR-195 in human placental trophoblast cells which reveals an invasion-promoting effect of the small RNA via repressing ActRIIA. Aberrant expression of miR-195 may contribute to the occurrence of preeclampsia through interfering with Activin/Nodal signaling mediated by ActRIIA in human placenta.
Highlights
MicroRNA is an endogenous,22 nucleotides non-coding small RNA with repression of proteins by seed sequence pairing to the untranslating region (39UTR) of target messenger RNAs [1]
The findings in the present study revealed that miR-195 could regulate trophoblast cells invasion via repressing ActRIIA protein expression, and down-regulation of the small molecule may be involved in the aberrant placenta function which contributes to the pathology of preeclampsia
There are no significant differences in age, body mass index (BMI), glucose tolerance, infant birth weight, and primiparous percentage between the normal pregnant and the preeclamptic women used in this study
Summary
MicroRNA is an endogenous ,22 nucleotides non-coding small RNA with repression of proteins by seed sequence pairing to the untranslating region (39UTR) of target messenger RNAs [1]. According to the prevailing model, microRNA can direct gene down-regulation by two posttranscriptional mechanisms: mRNA cleavage or translational repression. When 39UTR of target mRNA has perfect complementary to microRNA, it will specify cleavage or it will repress the productive translation when it has imperfect complementary [2]. It is well known that microRNA can regulate almost one third of human genes [5]. MiR-195 was found to be down-regulated in preeclamptic placentas compared with normal pregnant ones, indicating possible association of this small molecule with placental pathology of preeclampsia. By far the function of miR195 in the development of placenta remains unknown
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