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Chunk #43 — DISCUSSION

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Dysregulation of miR-34a links neuronal development to genetic risk factors for bipolar disorder.
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our study are strongly linked to neuronal structure and function. Not surprisingly, when we analyzed miR-34a predicted targets for gene ontology parameters, we found that molecular networks related to neuronal development, differentiation and synaptic plasticity were among the top significant results (Tables S3–S6). In addition, the same in silico analysis revealed autism together with schizophrenia and depressive disorder among the top five diseases enriched in miR-34a predicted targets (Table S7). The validation of miR-34a targets through luciferase assays was supported by correlation data between miR-34a and its mRNA targets ANK3 and CACNB3. Despite these negative correlations it is very likely that additional miRNAs or additional factors could be responsible for the changes in the levels of the targets during development66. It has also to be taken into account, though, that miRNAs and their targets are often in complex regulatory loops and the impact of miRNA-mediated inhibition can vary coherent and incoherent interactions3, 67, 68, so that anti-correlated expression is not a prerequisite for miRNA targeting.