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Endocrine Abstracts (2014) 34 OC2.6 | DOI: 10.1530/endoabs.34.OC2.6

SFEBES2014 Oral Communications Endocrine regulation of cell behaviour (6 abstracts)

A potential role for food-derived microRNAs in human placental development

Kate Timms , Melissa Westwood & Karen Forbes

University of Manchester, Manchester, UK.

Normal placental and fetal growth are important for neonatal and lifelong health. Placental growth is influenced by endogenous microRNAs (miRs) which regulate translation of their target genes into proteins. Recently, plant miRs from ingested food have been detected in mammalian circulation; maternal fruit and vegetable intake is important for normal development but the underlying mechanisms are not well understood. We hypothesised that miRNAs from maternal dietary fruit and vegetables influence placental growth and therefore investigated whether plant-specific miR-168a has a role in the human placenta.

Using QPCR, miR-168a was found to be present in human maternal serum and placenta. Bioinformatic analysis revealed that multiple components of the epidermal growth factor (EGF) signalling pathway, including the EGF receptor (EGFR), were putative miR-168a targets. EGFR is known to regulate both basal and EGF-stimulated placental growth. The potential role of miR-168a in regulating placental EGFR signalling was assessed using miR-168a mimics (50 nM) to overexpress miR-168a in BeWo choriocarcinoma cells (371-fold increase, P<0.05). Western blotting and QPCR revealed that miR-168a overexpression resulted in reduced EGFR protein (62%; P<0.05), but not mRNA expression, consistent with known miR actions. Immunofluorescence of the cell cyle marker, Ki67, showed that overexpression of miR-168a decreased both basal (53%; P<0.05) and EGF-stimulated (10 nM EGF; 50%; P<0.05) BeWo proliferation, consistent with a role for miR-168a in regulating EGFR mediated growth.

In summary, plant-specific miR-168a is present in maternal serum and can be detected in human placenta. The ability of dietary plant-derived miRs to influence gene expression and growth factor actions in human cells and tissue warrants further exploration. Our study suggests that they may have a role in regulating human placental development. Furthermore, the use of miR-168a mimics may have therapeutic potential in cancers and other diseases characterised by dysregulated EGF signalling.

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