title: Dicer-dependent miRNAs provide an endogenous restraint on cytotrophoblast proliferation.
abstract: Mature microRNAs (miRNAs) are processed from non-functional (pre)-miRNAs by the enzyme Dicer. In this study, manipulation of Dicer level was used to explore the influence of miRNAs on cytotrophoblast proliferation in human placenta. Immunohistochemistry (IHC) showed Dicer in cytotrophoblast, but not in terminally differentiated syncytiotrophoblast. siRNA-mediated knockdown of Dicer was used to effect a global reduction in miRNA in first trimester placental explants, as a result of which cytotrophoblast proliferation was significantly enhanced. QPCR and IHC analysis following Dicer knockdown revealed that the expression of two nodal pro-mitogenic signalling molecules expressed within cytotrophoblast, ERK and SHP-2, was significantly enhanced. Studies are now required to identify individual miRNAs involved in regulating trophoblast proliferation.
authors.affiliation: University of Manchester, School of Biomedicine, Maternal and Fetal Health Research Centre, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK. karen.forbes@manchester.ac.uk
authors.forename: K
authors.initials: K
authors.lastname: Forbes
authors.forename: F
authors.initials: F
authors.lastname: Farrokhnia
authors.forename: J D
authors.initials: JD
authors.lastname: Aplin
authors.forename: M
authors.initials: M
authors.lastname: Westwood
mesh_terms: D049109:Cell Proliferation; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000502:physiology*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology / Q000502:physiology
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D043244:Ribonuclease III