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PMID: 20065103 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

MiR-205 silences MED1 in hypoxic primary human trophoblasts.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology ·Vol. 24 ·No. 6 ·2010-06-00 ·Pages 2030-9

Mouillet JF, Chu T, Nelson DM, Mishima T, Sadovsky Y

Abstract

Acting through degradation of target mRNA or inhibition of translation, microRNAs (miRNAs) regulate development, differentiation, and cellular response to diverse cues. We analyzed changes in miRNA expression in human placental trophoblasts exposed to hypoxia, which may result from hypoperfusion and placental injury. Using an miRNA microarray screen, confirmed by Northern blot analysis, we defined a set of seven miRNAs (miR-93, miR-205, miR-224, miR-335, miR-424, miR-451, and miR-491) that are differentially regulated in primary trophoblasts exposed to hypoxia. We combined in silico prediction of miRNA targets with gene expression profiling data to identify a series of potential targets for the miRNAs, which were further analyzed using luciferase reporter assays. Among experimentally confirmed targets, we found that the transcriptional coactivator MED1, which plays an important role in placental development, is a target for miR-205. Using gain- and loss-of-function assays, we confirmed that miR-205 interacts with a specific target in the 3'-UTR sequence of MED1 and silences MED1 expression in human trophoblasts exposed to hypoxia, suggesting that miR-205 plays a role in trophoblast injury.

MeSH Terms
3' Untranslated Regions/genetics Blotting, Northern Blotting, Western Female Gene Expression Profiling Humans Hypoxia In Situ Hybridization Luciferases/metabolism Mediator Complex Subunit 1/antagonists & inhibitors,genetics,metabolism MicroRNAs/physiology Placenta/metabolism Pregnancy RNA, Messenger/genetics,metabolism Trophoblasts/physiology
Chemicals
3' Untranslated Regions MED1 protein, human MIRN205 microRNA, human Mediator Complex Subunit 1 MicroRNAs RNA, Messenger Luciferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mouillet Jean-Francois
Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA 15213, USA.
Chu Tianjiao
Nelson D Michael
Mishima Takuya
Sadovsky Yoel
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Article Info
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Abbr.
FASEB J
ISSN
1530-6860
DOI
10.1096/fj.09-149724
Published
2010-06-00
Epub
2010-00-11
Pages
2030-9
Language
English
Region
United States
NLM ID
8804484
PMCID
PMC2874470
Subset
IM
Grants
NICHD NIH HHS · R01-HD29190 · United States
NICHD NIH HHS · R01-HD45675 · United States
NICHD NIH HHS · R21-HD053878 · United States
NICHD NIH HHS · R01 HD045675 · United States
NICHD NIH HHS · R01 HD029190 · United States
NICHD NIH HHS · R21 HD053878 · United States
External Links
PubMed source DOI: 10.1096/fj.09-149724 PMC Full Text View journal details
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