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MiR‐205 silences MED1 in hypoxic primary human trophoblasts
Author(s) -
Mouillet JeanFrancois,
Chu Tianjiao,
Nelson D. Michael,
Mishima Takuya,
Sadovsky Yoel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-149724
Subject(s) - microrna , biology , microbiology and biotechnology , microarray , in silico , trophoblast , microarray analysis techniques , hypoxia (environmental) , gene expression profiling , three prime untranslated region , gene expression , bioinformatics , untranslated region , messenger rna , genetics , gene , placenta , chemistry , fetus , pregnancy , oxygen , organic chemistry
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.—Mouillet, J.‐F., Chu, T., Nelson, D. M., Mishima, T., Sadovsky, Y. MiR‐205 silences MED1 in hypoxic primary human trophoblasts. FASEB J. 24, 2030–2039 (2010). www.fasebj.org