Systematic review: Association between circulating microRNA expression & stroke

Abstract

This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of microRNA expression in the diagnosis and prognosis of ischaemic or haemorrhagic stroke. Electronic databases were searched from 1993 to October 2021, using key words relevant to concepts of stroke and microRNA. Studies that met specific inclusion and exclusion criteria were selected for data extraction. To minimise erroneous associations, findings were restricted to microRNAs reported to change in more than two independent studies. Of the papers assessed, 155 papers reported a change in microRNA expression observed in more than two independent studies. In ischaemic studies, two microRNAs were consistently differentially expressed in clinical samples (miR-29b & miR-146a) and four were altered in preclinical samples (miR-137, miR-146a, miR-181b & miR-223-3p). Across clinical and preclinical haemorrhagic studies, four microRNAs were downregulated consistently (miR-26a, miR-126, miR-146a & miR-155). Across included studies, miR-126 and miR-146a were the only two microRNAs to be differentially expressed in clinical and preclinical cohorts following ischaemic or haemorrhagic stroke. Further studies, employing larger populations with consistent methodologies, are required to validate the true clinical value of circulating microRNAs as biomarkers of ischaemic and haemorrhagic stroke.

Keywords: Biomarkers; haemorrhagic; ischaemic; microRNAs; stroke.

Figure 1.

Strategy implemented in the focused literature search and screening process. Papers were selected based on a set of inclusion and exclusion criteria. Following further comprehensive review, papers that lacked a method of qualitative analysis, such as qRT-PCR, were excluded from final analysis; this yielded 353 papers. Of these, 155 reported a change in microRNA expression in more than two independent studies.

Figure 2.

MicroRNA expression in included ischaemic clinical and preclinical studies. Diagrammatic representation of microRNA expression extracted from included ischaemic (a) clinical and (b) preclinical studies. Direction of change is indicated by colour; green – downregulation, orange – upregulated and lilac – no change. Circle size represents the number of included studies which reported expression. Constructed using Base R = R Core Team (2020) Vienna, Austria.

Figure 3.

MicroRNA expression in included haemorrhagic clinical and preclinical studies. Diagrammatic representation of microRNA expression extracted from included haemorrhagic clinical and preclinical studies. Direction of change is indicated by colour; green – downregulation and orange – upregulated. Circle size represents the number of included studies reporting expression. Constructed using Base R = R Core Team (2020) Vienna, Austria.