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. 2018 Mar 8;19(3):770. doi: 10.3390/ijms19030770

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© 2018 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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miRNA-34a in bipolar disease. miRNA-34a expression levels were selectively increased in the cerebellum from bipolar disease (BD) patients when compared to controls (Ctr) or patients that had received lithium treatment. Bioinformatic analysis predicted 25 miR-34a target genes including the GWAS loci ANK3, KLC2, CACNA1C, CACNB3, TENM4, and DDN. Transient reporter assays showed that miR-34a overexpression does silence ANK3, CACNA1C, and DDN expression. Conversely, inhibition of elevated miR-34a in neurons derived from BD iPSCs led to normalization of miR-34a target genes. In an orthogonal approach, Bavamian et al. [67] investigated the effects of miR-34a overexpression across iPSC differentiation on a panel of 131 genes with a potential role in BD or neurodevelopment. Among 70 differentially expressed transcripts, fourteen were encoded by GWAS loci. Furthermore, the corresponding proteins of these risk loci formed a highly connected protein interaction network.