MicroRNA: Relevance to stroke diagnosis, prognosis, and therapy

Mirzaei, Hamed; Momeni, Fatemeh; Saadatpour, Leila; Sahebkar, Amirhossein; Goodarzi, Mohammad; Masoudifar, Aria; Kouhpayeh, Shirin; Salehi, Hossein; Mirzaei, Hamid Reza; Jaafari, Mahmoud Reza

doi:10.1002/jcp.25787

Cited by 164 publications

(137 citation statements)

References 77 publications

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“…These small molecules can serve as diagnostic, prognostic and therapeutic biomarkers in various phases of IS [14]. Cellular miRNAs are easily degraded by ribonuclease in plasma as well as by RNaseA in vitro [34]; by contrast, miRNAs that bind to proteins of the Argonaute family or high-density lipoprotein particles or are included in microvesicles (exosomes and shedding vesicles) are protected from degradation in the circulation [35].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have found that they play key roles in the pathogenesis and pathology [12, 13] as well as in the complications and prognosis of stroke. Hence, these small molecules have emerged as novel diagnostic, prognostic, and therapeutic biomarkers in cerebral IS [14, 15]. However, none of these biomarkers have been utilized in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Wang

et al. 2018

Cerebrovasc Dis

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Background: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. Methods: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1–3 and days 4–7); one for the subacute phase IS (SIS, days 8–14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. Results: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1–3) were lower than that in controls (p < 0.05). In AIS (days 1–3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570–0.859, p = 0.007), 0.734 for RIS (95% CI 0.596–0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665–0.988, p = 0.001), 0.438 for AIS (days 1–3; 95% CI 0.240–0.635, p = 0.516). Conclusions: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Wang

et al. 2018

Cerebrovasc Dis

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“…Several studies have demonstrated significant alterations in the cerebral "miRNA-ome" following ischemia [14,15]. These reports suggest that miRNAs may act as innovative gene therapeutic candidates contributing to neurogenesis, angiogenesis, and neural plasticity [16,17]. A clinical study found that miR-30d-5p was downregulated in the brain cortex after hypoxia-ischemia and this miRNA is known to play an important role in regulation of autophagy and apoptosis in developing rat brains after hypoxic-ischemic injury [18].…”

Section: Introductionmentioning

confidence: 99%

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Jiang

Wang

Jin

et al. 2018

Cell Physiol Biochem

229

170

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Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

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“…miRNAs are short noncoding RNAs that act as main regulators in several cellular and molecular processes, such as angiogenesis, growth, differentiation, and development . It has been shown that deregulation of miRNAs is associated with the progression of various diseases, such as cancer, cardiovascular diseases, stroke, diabetes, and degenerative disorders . Based on the growing relevance of miRNAs in the regulation of MMPs, it is pertinent to point out that targeting of miRNAs regulating MMPs can be favorably used to blunt tumor progression or halt metastasis.…”

Section: Matrix Metalloproteinases: Their Functional Role In Cancermentioning

confidence: 99%

Micro‐RNAs as critical regulators of matrix metalloproteinases in cancer

Noruzi

Azizian

Mohammadi

et al. 2018

J of Cellular Biochemistry

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Metastasis is known to be one of the important factors associated with cancer-related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre-pro-growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro-RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro-RNAs, including miR-9, Let-7, miR-10b, and miR-15b, affects metastasis of tumor cells via targeting MMPs.

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MicroRNA: Relevance to stroke diagnosis, prognosis, and therapy

Cited by 164 publications

References 77 publications

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

Micro‐RNAs as critical regulators of matrix metalloproteinases in cancer

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