Circulating miR-155 and JAK2/STAT3 Axis in Acute Ischemic Stroke Patients and Its Relation to Post-Ischemic Inflammation and Associated Ischemic Stroke Risk Factors

Abstract

Background “Micro RNAs and their target genes recently have been identified to play a crucial role in the molecular pathogenesis of post-stroke ischemic cellular injury, which elucidates their new role in ischemic stroke diagnosis and therapy”. Thus, we evaluated the relative serum expression of miR-155, an inflammatory micro RNA, and the mRNAs (JAK2/STAT3) in acute ischemic stroke patients and its associations with the inflammatory cytokine TNF-α and different stroke risk factors. Subjects and Methods The relative expression of serum miR-155 and mRNAs (JAK2/STAT3) was assessed using RT-PCR, serum TNF-α was measured using ELIZA in 46 acute ischemic stroke patients and 50 control subjects. Receiver operating characteristic (ROC) curve was constructed to assess the specificity and sensitivity of circulating miR-155, JAK2/STAT3 as biomarkers for acute ischemic stroke. Results Circulating miR-155, JAK2/STAT3 were significantly up-regulated among stroke patients (8.5, 2.9, 4.2 fold respectively, P <0.001) with significant increase in TNF-α (263.8 ± 10.7 pg/mL, P <0.001). MiR-155, JAK2/STAT3 were positively correlated with TNF-α. MiR-155, JAK2/STAT3 were significantly increased in stroke patients and associated with risk factors such as hypertension, carotid atherosclerosis, and atrial fibrillation. Our study revealed that miR-155 has diagnostic accuracy for acute ischemic stroke where AUC=0.9, ( P <0.001). Conclusion The elevated expressions of circulating miR-155, JAK2/STAT3, and TNF-α in acute ischemic stroke patients could trigger post-stroke cellular inflammation. MiR-155 could be used as potential inflammatory biomarker for acute ischemic stroke. However, further clinical studies are still needed to determine the exact role of miRNAs and different signal transduction expressions in the stage of acute ischemic stroke.

MiR-155: An Important Regulator of Neuroinflammation

“…The increase in miR-155 expression was associated with a significant increase in JAK2/STAT3 expression in correlation with increased levels of TNF-α. It has been shown that these high levels of expression could trigger post-stroke cell inflammation and miR-155 could be used as a potential inflammatory biomarker for the acute phase of IS [ 93 ].…”

Bioinformatics analysis and experimental validation revealed that Paeoniflorigenone effectively mitigates cerebral ischemic stroke by suppressing oxidative stress and inflammation

“…The involvement of the JAK2/STAT3 pathway is crucial in the pathological process underlying ischemic stroke 43 , 44 . The increased expression of JAK2/STAT3 observed in individuals suffering from acute ischemic stroke may contribute to cellular inflammation 45 . IL-17 plays an important role in contributing to secondary damage and inflammation in post-ischemic stroke 46 .…”

Crosstalk between oxidative stress and neutrophil response in early ischemic stroke: a comprehensive transcriptome analysis

“…Previous experiments have observed that STAT3 expression levels were increased in the rat brain regions ipsilateral to middle cerebral artery occlusion (MCAO) relative to the sham group (15, 16). Moreover, Adly et al also found elevated levels of STAT3 in the peripheral blood of patients with IS compared to controls, indicating that STAT3 may act as a vital player in the pathogenesis of IS (17). Mechanically, Agrawal et al found that in an oxygen-glucose deprivation and reperfusion (OGD-R) model of PC12 cells, considerable reactive oxygen species (ROS) were generated, which could trigger the expression of STAT3 (18).…”

“…Moreover, Adly et al. also found elevated levels of STAT3 in the peripheral blood of patients with IS compared to controls, indicating that STAT3 may act as a vital player in the pathogenesis of IS ( 17 ). Mechanically, Agrawal et al.…”