Distinctive expression signatures of serum microRNAs in ischaemic stroke and transient ischaemic attack patients

Abstract

Circulating microRNAs (miRNAs) have recently emerged as promising biomarkers for ischaemic stroke (IS). However, the expression patterns of specific miRNAs in transient ischaemic attack (TIA) patients have not been investigated. Their predictive values for the presence of IS and TIA and their relationships to the neurological deficit severity of IS and the subsequent stroke risk after TIA remain unclear exactly. In this study, 754 miRNAs were initially screened by the TaqMan Low Density Array (TLDA) in two pooled serum samples from 50 IS patients and 50 controls. Markedly altered miRNAs were subsequently validated by individual quantitative reverse-transcription PCR (qRT-PCR) assays first in the same cohort of TLDA and further confirmed in another larger cohort including 177 IS, 81 TIA patients and 42 controls. Consequently, TLDA screening showed that 71 miRNAs were up-regulated and 49 miRNAs were down-regulated in IS patients. QRT-PCR validation confirmed that serum levels of miR-23b-3p, miR-29b-3p, miR-181a-5p and miR-21-5p were significantly increased in IS patients. Strikingly, serum levels of miR-23b-3p, miR-29b-3p and miR-181a-5p were also significantly elevated in TIA patients. Furthermore, up-regulated miR-23b-3p, miR-29b-3p and miR-21-5p could clearly differentiate between IS and TIA patients. Logistic regression and receiver-operating characteristic curve analyses demonstrated that these altered miRNAs may function as predictive and discriminative biomarkers for IS and TIA, and their distinctive expression signatures may contribute to assessing neurological deficit severity of IS and subsequent stroke risk after TIA.

MicroRNAs as Diagnostic and Prognostic Biomarkers in Ischemic Stroke—A Comprehensive Review and Bioinformatic Analysis

“…Logistic regression and ROC curve analyses showed that these changed miRNAs may function as predictive and discriminative biomarkers for IS and TIA. Thus, authors suggested that, their distinctive expression signatures may contribute to assessing neurological deficit severity of IS and subsequent stroke risk after TIA [78].…”

Serum miRNA125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to differentiate between posterior circulation stroke and peripheral vertigo

“…This temporal expression pattern might be useful in elucidating the mechanism of miRNA involvement in the pathophysiology and pathogenesis of acute ischemic stroke. An elevation of serum miRNA in the acute phase of ischemic stroke is possibly due to the passive release from ischemia-vulnerable neurons [ 12 ] or by active secretion via extracellular vesicles [ 8 , 13 ].…”

SNHG12 inhibits oxygen‑glucose deprivation‑induced neuronal apoptosis via the miR‑181a‑5p/NEGR1 axis

“…There is ample evidence indicating that ischemic stroke is caused by intracranial thrombosis or extracranial embolism, resulting in a lack of blood flow and supply of oxygen and nutrients ( 4 , 19 , 31 ). Subsequently, multiple complex factors lead to the destruction of the blood-brain barrier following ischemic stroke, which further aggravates brain damage and a series of neurological events, including oxidative stress, toxicity of excitatory amino acids, excessively high calcium ion concentrations and increased apoptosis ( 4 , 31 , 32 ).…”

“…A previous study reported that miR-181a-5p levels were significantly increased in the serum of patients with ischemic stroke ( 18 ). However, few studies have been conducted on the role of miR-181a-5p in ischemic stroke and its regulatory mechanism ( 19 ). It has been demonstrated that a lncRNA, small nucleolar RNA host gene 12 (SNHG12), serves a critical role in ischemic stroke by acting as a ceRNA and competing with various miRNAs to regulate specific RNA transcription ( 20 , 21 ).…”