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Zhaowei Cai,Zhilan Xiao,Yufang Wang,Huazhen Liu,Kangdi Zhang,Xiaoning Zhen,Xiaoling Jiang 한국유전학회 2020 Genes & Genomics Vol.42 No.11
Background Down syndrome (DS), caused by trisomy 21, is the most common human chromosomal disorder. Hippocampalabnormalities have been believed to be responsible for the DS developmental cognitive deficits. Cumulative evidences indicatedthat non-coding RNAs (ncRNAs) participated in brain development and function. Currently, few was known whetherdysregulated ncRNAs existed in DS whether the dysregulated ncRNAs played important pathology roles in DS. Objective The purpose of this study was generating an overview map of the dysregulated ncRNAs in DS, including themicroRNA (miRNA), long ncRNA (lncRNA) and circular RNA (circRNAs). DS mouse models are invaluable tools forfurther mechanism and therapy studies. Methods The well-studied DS mouse model Dp(16)1/Yey was used in this study as it contains the trisomy of the whole humanchromosome 21 syntenic region on mouse chromosomes 16. Hippocampi were isolated from pups of seven-days-old. Librariesfor miRNA, lncRNA and circRNAs were constructed separately, and the next generation sequencing method was utilized. Results Differentially expressed (DE) miRNAs, lncRNAs and circRNAs were reported. Relative few regulating relationshipwere found between the DE miRNAs and DE mRNAs. LncRNAs originated from the trisomic regions expressed in clusters,but not all of them were 1.5-fold increased expressed. Dramatic DE circular RNAs were found in the DS hippocampus. The host genes of the DE circRNAs were enriched on functions which were well-known impaired in DS, e.g. long-termpotentiation,glutamatergic synapse, and GABAergic synapse. Conclusions We generated the first DS developmental hippocampal ncRNA transcriptome map. This work laid foundationsfor further investigations on role of ncRNAs in hippocampal functions.