PMID- 27577708
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20180503
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 45
DP  - 2016 Sep
TI  - HLA-G expression is regulated by miR-365 in trophoblasts under hypoxic 
      conditions.
PG  - 37-41
LID - S0143-4004(16)30156-4 [pii]
LID - 10.1016/j.placenta.2016.07.004 [doi]
AB  - INTRODUCTION: Hypoxia occurs in the first trimester of placental development and 
      is implicated in the regulation of trophoblast differentiation. Prolonged hypoxic 
      conditions in the placenta are related to the development of preeclampsia. 
      MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that modulate gene 
      expression by targeting messenger RNA. We hypothesized that, under hypoxic 
      conditions, trophoblasts may have a unique miRNA profile that may play a critical 
      role in placental development. METHODS: Total RNA was extracted from human 
      trophoblast, HChEpC1b, exposed to normoxia (20% O2) or hypoxia (2% O2) for 24 h, 
      and the miRNA expression profiles were investigated using a microRNA array. 
      Several differential miRNAs were selected and validated using real-time reverse 
      transcription PCR. We identified potential targets of these miRNAs using in 
      silico analysis. We confirmed a potential target protein by western blot analysis 
      and luciferase assays. RESULTS: The expression of miR-365 was significantly 
      upregulated under hypoxic conditions. In silico analysis showed that miR-365 
      targeted human leukocyte antigen (HLA)-G. Both hypoxic conditions and 
      overexpression of miR-365 inhibited the expression of HLA-G proteins. The 
      overexpression of miR-365 also decreased the activity of the luciferase reporter 
      containing the 3'-untranslated region (UTR) of HLA-G with the predicted 
      miR-365-binding site. DISCUSSION: HLA-G is a non-classical HLA class-Ib molecule 
      that is expressed mainly in extravillous trophoblasts and which plays a key role 
      in maintaining immune tolerance at the maternal-fetal interface. Our results 
      indicate that miR-365 targets the HLA-G 3' UTR to repress its expression. The 
      expression of miR-365 may play an important role in human placental development 
      and in immunoprotection of the semiallogenic embryo.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Mori, Asako
AU  - Mori A
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan.
FAU - Nishi, Hirotaka
AU  - Nishi H
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan. 
      Electronic address: nishih@tokyo-med.ac.jp.
FAU - Sasaki, Toru
AU  - Sasaki T
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan.
FAU - Nagamitsu, Yuzo
AU  - Nagamitsu Y
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan.
FAU - Kawaguchi, Rie
AU  - Kawaguchi R
AD  - Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 
      Tokyo, Japan.
FAU - Okamoto, Aikou
AU  - Okamoto A
AD  - Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 
      Tokyo, Japan.
FAU - Kuroda, Masahiko
AU  - Kuroda M
AD  - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
FAU - Isaka, Keiichi
AU  - Isaka K
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160721
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (3' Untranslated Regions)
RN  - 0 (HLA-G Antigens)
RN  - 0 (MIRN365 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Cell Communication
MH  - Cell Hypoxia/*physiology
MH  - Female
MH  - Gene Expression Regulation
MH  - HLA-G Antigens/genetics/*metabolism
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Placenta/cytology/metabolism
MH  - Placentation/*physiology
MH  - Pregnancy
MH  - Trophoblasts/cytology/*metabolism
OTO - NOTNLM
OT  - HLA-G
OT  - Hypoxia
OT  - Placenta
OT  - miR-365
OT  - miRNA
EDAT- 2016/09/01 06:00
MHDA- 2017/12/08 06:00
CRDT- 2016/09/01 06:00
PHST- 2016/03/02 00:00 [received]
PHST- 2016/07/11 00:00 [revised]
PHST- 2016/07/19 00:00 [accepted]
PHST- 2016/09/01 06:00 [entrez]
PHST- 2016/09/01 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
AID - S0143-4004(16)30156-4 [pii]
AID - 10.1016/j.placenta.2016.07.004 [doi]
PST - ppublish
SO  - Placenta. 2016 Sep;45:37-41. doi: 10.1016/j.placenta.2016.07.004. Epub 2016 Jul 
      21.