C19MC microRNAs regulate the migration of human trophoblasts

Lan Xie, Jean Francois Mouillet, Tianjiao Chu, W. Tony Parks, Elena Sadovsky, Martin Knöfler, Yoel Sadovsky*

*Corresponding author for this work

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Early in pregnancy, trophoblast invasion into the decidua and inner myometrium is essential for establishment of proper implantation, maternal-fetal exchange, and immunological tolerance of the feto-placental allograft. Unlike villous trophoblasts (VTs), extravillous trophoblasts (EVTs) are unique in their capacity to invade the maternal decidua and myometrium. The largest human microRNA (miRNA) gene cluster, the chromosome 19 miRNA cluster (C19MC), is expressed almost exclusively in the placenta and, rarely, in certain tumors and undifferentiated cells. In the work reported here, we found that the expression of C19MC miRNAs is higher in VTs than in EVTs. Using a bacterial artificial chromosome (BAC)-mediated overexpression of C19MC miRNAs in an EVT-derived cell line, which does not naturally express these miRNAs, we found that C19MC miRNAs selectively attenuate cell migration without affecting cell proliferation or apoptosis. A microarray analysis revealed that C19MCmiRNAs regulate target transcripts related to cellular movement. Our data also implicated a specific C19MC member, miR-519d, indirectly regulating the EVT invasive phenotype by targeting CXCL6, NR4A2 and FOXL2 transcripts through a 3′UTR miRNA-responsive element. Together, our data suggest a role for C19MCmiRNAsin modulating the migration of EVTs.

Original languageEnglish (US)
Pages (from-to)4975-4985
Number of pages11
JournalEndocrinology
Volume155
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Endocrinology

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    Xie, L., Mouillet, J. F., Chu, T., Parks, W. T., Sadovsky, E., Knöfler, M., & Sadovsky, Y. (2014). C19MC microRNAs regulate the migration of human trophoblasts. Endocrinology, 155(12), 4975-4985. https://doi.org/10.1210/en.2014-1501