Circular RNA expression alterations are involved in OGD/R-induced neuron injury.

Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.

Increased expression of microRNA-21 in peripheral blood mediates the down-regulation of IFN-γ and increases the prevalence of stroke-associated infection.

BACKGROUND: Increasing levels of microRNA (miRNA)-21 can lead to IFN-γ deficiency, thereby suppressing immune function. Whether changes in the peripheral blood expression of miRNA-21 in patients with acute stroke are related to stroke-associated infection (SAI) remains unsettled. METHODS: MiRNA-21 and IFN-γ expression levels in peripheral blood plasma were measured in stroke patients presenting within 24h of symptom onset to assess whether these expression levels are associated with the prevalence of SAI. RESULTS: The stroke with SAI group had significantly higher miRNA-21 expression and lower IFN-γ levels than the stroke without SAI group (p<0.05). A significant negative correlation was observed between miRNA-21 expression and IFN-γ levels (r=-0.303, p=0.026). ROC curves were constructed to measure the performance of the miRNA-21 and IFN-γ to judge SAI. The areas under the ROC curve (AUC) for miRNA-21 and IFN-γ were 0.667 (95% CI, 0.525 to 0.798, p=0.028) and 0.698 (95% CI, 0.558 to 0.816, p=0.005), respectively. The optimal cutoff value was miRNA-21>0.53 and IFN-γ≤72.57pg/ml. There was a significantly different prevalence of SAI between the high miRNA-21 group and the low miRNA-21 group (p=0.008, log rank test). There was also a significant difference between the high IFN-γ group and the low IFN-γ group (p=0.003, log rank test). CONCLUSIONS: Plasma up-regulated miRNA-21 and decreased IFN-γ in acute stroke can be considered new biological predictors for SAI and thus, new therapeutic targets.