Downregulated miR-195 detected in preeclamptic placenta affects trophoblast cell invasion via modulating ActRIIA expression.
BACKGROUND
Preeclampsia (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.


RESULTS
Bioinformatic 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
This 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.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Yang
Y
Bai
Weiwei
W
Yang
Hui-xia
HX
Yang
Qinping
Q
Liao
Gang
G
Ye
Guodong
G
Fu
Lei
L
Ji
Peng
P
Xu
Hao
H
Wang
Yu-xia
YX
Li
Chun
C
Peng
Yan-ling
YL
Wang
D030301:Activin Receptors, Type II / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D056743:Cyclin D3; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A