Abstract

Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p. The results suggest that the blood level of let-7e-5p was significantly higher in patients with ischemic stroke than in controls (p<0.05). Higher levels of let-7e-5p were associated with increased occurrence of ischemic stroke (adjusted OR, 1.89; 95% CI, 1.61~2.21, p<0.001) in the combined population. The addition of let-7e-5p to traditional risk factors led to an improvement in the area under the curve, which increased from 0.74 (95% CI, 0.70~0.78) to 0.82 (95% CI, 0.78~0.85), with a net reclassification improvement of 16.76% (p<0.0001) and an integrated discrimination improvement of 0.10 (p<0.0001) for patients with ischemic stroke. Bioinformatics prediction and cell experiments suggested that the expression levels of four genes enriched in the MAPK signaling pathway were down-regulated by let-7e-5p transfection. Specifically, the expression levels of the genes CASP3 and NLK were significantly lower in ischemic stroke patients than in controls and were negatively correlated with let-7e-5p expression. In summary, our study suggests the potential use of blood let-7e-5p as a biomarker for ischemic stroke and indicates its involvement in the related pathomechanism.

Highlights

  • Stroke is the second leading cause of death in people more than 60 years old, and it is the fifth leading cause of death in people between 15 and 59 years old [1]

  • FG, fasting glucose; TC, total cholesterol; TG, triglycerides; HDL-C, highdensity lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; platelet count value (PLT), blood platelet; PDW, platelet distribution width; MPV, mean platelet volume; PCT, plateletcrit. * Student’s t test for the difference between ischemic stroke patients and controls. † Chi-square test for the difference in the distribution frequencies between ischemic stroke patients and controls. ‡ Mann–Whitney U test for the differences between ischemic stroke patients and controls

  • The results showed that higher levels of let-7e-5p were associated with an increased risk of ischemic stroke after adjusting for conventional risk factors, including age, sex, smoking, drinking, history of hypertension and diabetes mellitus

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Summary

Objectives

We aimed to determine whether the whole blood level of let-7e-5p is differentially expressed in patients with ischemic stroke

Methods
Results
Conclusion

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