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  • Title: MiR-199a-5p regulates sirtuin1 and PI3K in the rat hippocampus with intrauterine growth restriction.
    Author: Chen J, Gong X, Huang L, Chen P, Wang T, Zhou W, Luo K, Wang J.
    Journal: Sci Rep; 2018 Sep 14; 8(1):13813. PubMed ID: 30217997.
    Abstract:
    In humans, malnutrition during pregnancy results in intrauterine growth restriction (IUGR) and an increased risk of neurological morbidities; altered miRNA characteristics have been suggested to contribute to IUGR neurological pathogenesis. A miRNA microarray was used to identify differentially expressed miRNA molecules in the hippocampi of rats with IUGR. Five of the molecules in question were selectively validated using real-time PCR in rats with IUGR. We then investigated the role of miR-199a-5p in hippocampal pathology. Bioinformatics analysis results suggested that TNF-α, caspase-3 and SIRT1 were potential targets of miR-199a-5p. Changes in PI3K, SIRT1 and caspase-3 protein expressions levels in the hippocampus were confirmed by Western blot analysis (all P < 0.05). Studies using the pheochromocytoma cell line PC12 cells and primary neurons demonstrated that miR-199a-5p modulated PI3K, caspase-3 and SIRT1 expression. Additionally, there was an inverse correlation between miR-199a-5p and caspase-3 expression, though dual-luciferase reporter assays showed that caspase-3 is not a target of miR-199a-5p. We conclude that IUGR affects hippocampal miRNAs characteristics. Our results also indicated that aberrantly high expression levels of miR-199a-5p may play an important role in the pathogenesis of IUGR by regulating SIRT1 and PI3K.
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