title: Identification of Blood Let-7e-5p as a Biomarker for Ischemic Stroke.
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.
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Suli
authors: S
authors: Huang
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Ziquan
authors: Z
authors: Lv
authors: Department of Neurology, People's Hospital of Shenzen, Guangdong, China.
authors: Yi
authors: Y
authors: Guo
authors: Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Lu
authors: L
authors: Li
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Yanwei
authors: Y
authors: Zhang
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Li
authors: L
authors: Zhou
authors: State Key Lab of Respiratory Disease, Institute for Chemical Carcinogenesis, School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors: Binyao
authors: B
authors: Yang
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Shuang
authors: S
authors: Wu
authors: Department of Neurology, People's Hospital of Shenzen, Guangdong, China.
authors: Ying
authors: Y
authors: Zhang
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Changhui
authors: C
authors: Xie
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Shanshan
authors: S
authors: Li
authors: Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
authors: Jinquan
authors: J
authors: Cheng
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002545:Brain Ischemia / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D020521:Stroke / Q000235:genetics*; D020298:U937 Cells
chemical_list: D015415:Biomarkers; D035683:MicroRNAs