Borna disease virus infection impacts microRNAs associated with nervous system development, cell differentiation, proliferation and apoptosis in the hippocampi of neonatal rats

摘要

MicroRNAs (miRNAs) regulate gene expression by inhibiting transcription or translation and are involved in diverse biological processes, including development, cellular differentiation and tumor generation. miRNA microarray technology is a high-throughput global analysis tool for miRNA expression profiling. Here, the hippocampi of four borna disease virus (BDV)-infected and four non-infected control neonatal rats were selected for miRNA microarray and bioinformatic analysis. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis was subsequently performed to validate the dysregulated miRNAs. Seven miRNAs (miR-145*, miR-146a*, miR-192*, miR-200b, miR-223*, miR-449a and miR-505), showed increased expression, whereas two miRNAs (miR-126 and miR-374) showed decreased expression in the BDV-infected group. By RT-qPCR validation, five miRNAs (miR-126, miR-200b, miR-374, miR-449a and miR-505) showed significantly decreased expression (P< 0.05) in response to BDV infection. Biocarta pathway analysis predicted target genes associated with 'RNA', 'IGF1mTOR', 'EIF2', 'VEGF', 'EIF', 'NTHI', 'extrinsic', 'RB', 'IL1R' and 'IGF1' pathways. Gene Ontology analysis predicted target genes associated with 'peripheral nervous system development', 'regulation of small GTPase-mediated signal transduction', 'regulation of Ras protein signal transduction', 'aerobic respiration', 'membrane fusion', 'positive regulation of cell cycle', 'cellular respiration', 'heterocycle metabolic process', 'protein tetramerization' and 'regulation of Rho protein signal transduction' processes. Among the five dysregulated miRNAs identified by RT-qPCR, miR-126, miR-200b and miR-449a showed a strong association with nervous system development, cell differentiation, proliferation and apoptosis.