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Genome-wide analysis of the circulating miRNome after cerebral ischemia reveals a reperfusion-induced microRNA cluster

ABSTRACT: Background and Purpose - Circulating microRNAs (miRNAs) are emerging biomarkers for stroke due to their high stability in the bloodstream and association with pathophysiologic conditions. However, the circulating whole-genome miRNAs (miRNome) has not been characterized comprehensively in the acute phase of stroke. Methods - We profiled the circulating miRNome in mouse models of acute ischemic and hemorrhagic stroke by next-generation sequencing (NGS). Stroke models were compared to sham-operated and naïve mice to identify deregulated circulating miRNAs. Top-ranked miRNAs were validated and further characterized by qRT-PCR. Results - We discovered 24 circulating miRNAs with an altered abundance in the circulation 3 hours following ischemia, whereas the circulating miRNome was not altered after intracerebral hemorrhage compared to sham-operated mice. Among the upregulated miRNA in ischemia, the top-listed miR-1264/1298/448 cluster was strongly dependent on reperfusion in different ischemia models. A time course experiment revealed that the miR-1264/1298/448 cluster peaked in the circulation around 3 hours after reperfusion and gradually decreased thereafter. Conclusions - Alteration of the miRNome in the circulation is associated with cerebral ischemia/reperfusion, but not hemorrhage, suggesting a potential to serve as biomarkers for reperfusion in the acute phase. The pathophysiological role of reperfusion-inducible miR-1264/1298/448 cluster, which is located on chromosome X within the introns of the serotonin receptor HTR2C, requires further investigation.

ORGANISM(S): Mus musculus

PROVIDER: GSE84216 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA328393

REPOSITORIES: GEO

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