Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges

• DOI: 10.1186/s12864-015-2160-6
• Publication Date: 2015-11-06T07:59:19Z
• Authors: Xavier Bofill-De Ros; Mónica Santos; Maria Vila-Casadesús; Eneko Villanueva; Nuria Andreu; Mara Dierssen; Cristina Fillat
• Keywords: Identification

Down syndrome (DS) or trisomy 21 is the result of a genetic dosage imbalance that translates in broad clinical spectrum. A major challenge study DS identification functional elements with wide impact on phenotypic alterations. Recently, miRNAs have been recognized as contributors to several disease conditions by acting post-transcriptional regulators plethora genes. Five chromosome (HSA21) found overexpressed individuals and could function key pathophysiology. Interestingly, trisomic Ts65Dn mouse model two these (miR-155 miR-802) are also triplicated brain.In current work, we interrogated miR-155 miR-802 upregulation transcriptome brains. We developed lentiviral miRNA-sponge strategy (Lv-miR155-802T) identify vivo relevant target mRNAs. Hippocampal injections sponges mice normalized expression rescued levels their targets methyl-CpG-binding protein 2 gene (Mecp2), SH2 (Src homology 2)-containing inositol phosphatase-1 (Ship1) Forkhead box M1 (FoxM1). Transcriptomic data Lv-miR155-802T treated hippocampi correlated candidate highlighting miRNA dosage-sensitive Significant associations were subset genes (Rufy2, Nova1, Nav1, Thoc1 Sumo3) be experimentally validated.The demonstrated genome-wide regulatory effects miR-802. Furthermore, analysis combining predicted candidates experimental transcriptomic proved retrieve potential significance DS-hippocampal phenotype bridging other neurological-associated diseases such Alzheimer's disease.