Hydroxysteroid (17-β) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia.
In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70-36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE.
Department of Molecular Medicine and Anatomy, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8602, Japan.
Osamu
O
Ishibashi
Akihide
A
Ohkuchi
Md Moksed
MM
Ali
Ryuhei
R
Kurashina
Shan-Shun
SS
Luo
Tomoko
T
Ishikawa
Takami
T
Takizawa
Chikako
C
Hirashima
Kayo
K
Takahashi
Makoto
M
Migita
Gen
G
Ishikawa
Koichi
K
Yoneyama
Hirobumi
H
Asakura
Akio
A
Izumi
Shigeki
S
Matsubara
Toshiyuki
T
Takeshita
Toshihiro
T
Takizawa
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis* / Q000378:metabolism*; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D015415:Biomarkers; C543800:MIRN210 microRNA, human; C571457:MIRN518 microRNA, human; D035683:MicroRNAs; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human