Plasma miR-124 as a biomarker for cerebral infarction

Weng, Huachun; Shen, Chun-Shen; Hirokawa, Gou; Ji, Xu; Takahashi, Rie; Shimada, Keisuke; Kishimoto, Chiharu; Iwai, Naoharu

doi:10.2220/biomedres.32.135

Cited by 120 publications

(92 citation statements)

References 30 publications

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“…[19][20][21][22][23][24] Recently, plasma miR-124 was found to be elevated in rats after cerebral ischemia, suggesting its potential role as biomarker for cerebral infarction. 25,26 miR-124 can target a large number of mRNAs, [27][28][29] such as cyclin-dependent kinase 6, laminin γ1, Lhx2, and Sox9. 21,[30][31][32] Hence, miR-124 may have multiple and complex roles in cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124–Mediated Regulation of Inhibitory Member of Apoptosis-Stimulating Protein of p53 Family in Experimental Stroke

Liu

Zhao

et al. 2013

Stroke

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Background and Purpose-p53-mediated neuronal death is a central pathway of stroke pathophysiology, but its mechanistic details remain unclear. Here, we identified a novel microRNA mechanism that downregulation of inhibitory member of the apoptosis-stimulating proteins of p53 family (iASPP) by the brain-specific microRNA-124 (miR-124) promotes neuronal death after cerebral ischemia. Methods-In a mouse model of focal permanent cerebral ischemia, the expression of iASPP and miR-124 was quantified by reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence staining, and Western blot. Luciferase reporter assay was used to validate whether miR-124 can directly bind to the 3′-untranslated region of iASPP mRNA. To evaluate the role of miR-124, miR-124 mimic and its inhibitor were transfected into Neuro-2a cells and C57 mice. Results-There was no change in the iASPP mRNA level in cerebral ischemia. However, iASPP protein was remarkably decreased, with a concurrent elevation in miR-124 level. Furthermore, miR-124 can bind to the 3′-untranslated region of iASPP in 293T cells and downregulate its protein levels in Neuro-2a cells. In vivo, infusion of miR-124 decreased brain levels of iASPP, whereas inhibition of miR-124 enhanced iASPP levels and significantly reduced infarction in mouse focal cerebral ischemia. Conclusions-These data demonstrate that p53-mediated neuronal cell death after stroke can be nontranscriptionally regulated by a novel mechanism involving suppression of endogenous cell death inhibitors by miR-124. Further dissection of microRNA regulatory mechanisms may lead to new therapeutic opportunities for preventing neuronal death after stroke.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-124–Mediated Regulation of Inhibitory Member of Apoptosis-Stimulating Protein of p53 Family in Experimental Stroke

Liu

Zhao

et al. 2013

Stroke

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“…At 0 and 6 h following ligation and sham operation (n = 5; each operation), rats were anesthetized with pentobarbital, and blood was collected for further miRNAs and CPK analysis. cardium-specific miRNAs are excellent biomarkers for myocardial infarction (1,22), and plasma concentrations of brain-specific miRNA can serve as a biomarker for cerebral infarction (38). In the present study, we focused on the miRNA expression in muscular tissues and assessed whether expression profiling of miRNAs in various muscle cells may be useful for the diagnosis of diseases involving muscle cells.…”

Section: Assessment Of Plasma Mirnas As Biomarkers For Muscular Injurmentioning

confidence: 99%

Classification of various muscular tissues using miRNA profiling

et al. 2013

Self Cite

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MicroRNAs (miRNAs) are endogenous small RNAs of 18-23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored whether miRNA expression profiling of various muscle cells may be useful for the diagnosis of various diseases involving muscle necrosis. miRNA expression profiling was assessed by miRNA array and real-time reverse-transcriptase polymerase chain reaction by using a reverse primer of a stem loop structure. Profiling of various muscle cells of mouse, including cardiac muscles, skeletal muscles, and vascular and visceral smooth muscles, indicated that profiling of miR-1, miR-133a, miR-133b, miR-145, miR-206, miR-208a, miR-208b, and miR-499 were adequate to discriminate muscle cells. miR-145 was remarkably highly expressed in smooth muscles. miR-208a and miR-499 were highly expressed in cardiomyocytes. miR-133a was highly expressed in fast-twitch skeletal muscles. miR-206 and miR-208b were expressed in the slow-twitch skeletal muscles, and they can likely discriminate fast-and slow-twitch types of skeletal muscle cells. We observed that brown fat adipose cells had an miRNA expression profile very similar to those of skeletal muscle cells in the mouse. Plasma concentrations of miR-133a and miR-145 were extremely useful in diagnosing skeletal muscle necrosis in a mouse model of Duchenne muscular dystrophy and colon smooth muscle necrosis in a rat ischemic colitis model, respectively. In the present study, we investigated the miRNA expression profiles of various muscular tissues. Our results suggest that expression profiling would be useful for the diagnosis of various diseases such as muscular necrosis.

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“…Jeyaseelan et al [16] demonstrated a large elevation in circulating miR-290 at 24 hours after reperfusion in rats subjected to middle cerebral artery occlusion. In similar rat models of stroke, Liu et al [17] demonstrated increases in miR-10a, miR-182, miR-200b and miR-298 in both blood and brain 24 hours following ischemia/ reperfusion [17], while Weng et al [137] measured an increase in plasma levels of miR-124 as early as 6 hours following reperfusion. Unfortunately these studies did not demonstrate changes in the miRNA profile in the period immediately following ischemia, prior to reperfusion, which would be clinically relevant in determining a diagnosis and instituting treatment in people suffering acutely from stroke.…”

Section: G Mirnas As Biomarkersmentioning

confidence: 98%

microRNAs: Innovative Targets for Cerebral Ischemia and Stroke

Yu¹,

Stary²,

Yang³

et al. 2012

CDT

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Stroke is one of the leading causes of death and disability worldwide. Because stroke is a multifactorial disease with a short therapeutic window many clinical stroke trials have failed and the only currently approved therapy is thrombolysis. MicroRNAs (miRNA) are endogenously expressed noncoding short single-stranded RNAs that play a role in the regulation of gene expression at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in ischemic disease. miRNAs are especially important candidates for stroke therapeutics because of their ability to simultaneously regulate many target genes and since to date targeting single genes for therapeutic intervention has not yet succeeded in the clinic. Although there are already quite a few review articles about miRNA in ischemic heart disease, much less is currently known about miRNAs in cerebral ischemia. This review summarizes current knowledge about miRNAs and cerebral ischemia, focusing on the role of miRNAs in ischemia, both changes in expression and identification of potential targets, as well as the potential of miRNAs as biomarkers and therapeutic targets in cerebral ischemia.

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Plasma miR-124 as a biomarker for cerebral infarction

Cited by 120 publications

References 30 publications

MicroRNA-124–Mediated Regulation of Inhibitory Member of Apoptosis-Stimulating Protein of p53 Family in Experimental Stroke

MicroRNA-124–Mediated Regulation of Inhibitory Member of Apoptosis-Stimulating Protein of p53 Family in Experimental Stroke

Classification of various muscular tissues using miRNA profiling

microRNAs: Innovative Targets for Cerebral Ischemia and Stroke

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