Abstract
Alzheimer's disease (AD) is a global health issue, but the precise underlying mechanism has not yet been elucidated. The present study aimed to integrate microRNA (miRNA or miR) and mRNA profiles of AD and identify hub genes via bioinformatics analysis. Datasets associated with AD (GSE113141, GSE104249 and GSE138382) were integrated. Bioinformatics analysis was used to identify the hub mRNAs. TargetScan was used to predict miRNAs that have binding sites for the hub genes. Reverse transcription‑quantitative (RT‑q)PCR and western blot analysis was performed to assess miRNA and mRNA expression levels in APP/PS1 transgenic mice and human U251 cells. Luciferase reporter assay and RNA interference were utilized to verify the functions of these miRNAs in vitro. Bioinformatics analysis demonstrated that expression levels of the gene encoding transmembrane immune signaling adaptor TYROBP were upregulated in both the GSE113141 and GSE104249 datasets; TYROBP also served as the hub gene in AD. miR‑628‑5p was predicted to have binding sites for TYROBP and was downregulated in GSE138382. RT‑qPCR confirmed low miR‑628‑5p and high TYROBP expression levels in APP/PS1 transgenic mice and human U251 cells. Western blot analysis demonstrated high protein expression levels of amyloid β (Aβ) precursor protein, Aβ and TYROBP in APP/PS1 transgenic mice and U251 cells. Dual luciferase reporter assay confirmed that TYROBP was targeted by miR‑628‑5p. miR‑628‑5p/TYROBP may inhibit progressive neurodegeneration in AD and could be used as novel biomarkers and candidate drug targets.