Altered Plasma MicroRNAs as Novel Biomarkers for Arteriosclerosis Obliterans

He, Xuemei; Zheng, Ying-Qiang; Liu, Sheng-Zhi; Liu, Yong; He, Yanzheng; Zhou, Xiangyu

doi:10.5551/jat.30775

Cited by 34 publications

(41 citation statements)

References 41 publications

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“…It has been proposed that hsa-miR-4306, hsa-miR-320e and hsa-miR-320d in plasma may serve as novel biomarkers for the early detection of acute stroke in humans [29]. miR-4306 were was shown to be significantly downregulated both in Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry plasma and in sclerotic samples of patients with arteriosclerosis obliterans compared with controls [30]. Our study indicates that hsa-miR-4306 in plasma was upregulated, whereas hsa-miR-320a was decreased 30 minutes following administration of dexmedetomidine.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, the fold-change and P-values thresholds were 1.2 and <0.1, respectively, which are different from those commonly accepted and were used here because of the relatively short time of exposure to dexmedetomidine. Secondly, some miRNAs are expressed in a time-and stage-specific manner [30]. Thus, the expression pattern of dysregulated miRNAs is not always constant and may fluctuate with time.…”

Section: Discussionmentioning

confidence: 99%

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Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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“…Cells with a myofibroblastic nature in the LF may be involved in the hypertrophy 22) , thus suggesting that miR-497-5p possibly plays a role in hypertrophy via the promotion of myofibroblast in LF. It has been reported that miR-4306 was significantly decreased in the sclerotic samples of patients with arteriosclerosis obliterans, characterized by fibrosis of the tunica intima 23) . Thus, these miRNAs may also play a role in the fibrotic change of LF.…”

Section: A B Cmentioning

confidence: 99%

MicroRNA transcriptome analysis on hypertrophy of ligamentum flavum in patients with lumbar spinal stenosis

Mori

Sakai²,

Kayano

et al. 2017

Spine Surg Relat Res

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Abstract:Introduction: Molecular pathways involved in ligamentum flavum (LF) hypertrophy are still unclarified. The purpose of this study was to characterize LF hypertrophy by microRNA (miRNA) profiling according to the classification of lumbar spinal stenosis (LSS).Methods: Classification of patients with LSS into ligamentous and non-ligamentous cases was conducted by clinical observation and the morphometric parameter adopting the LF/spinal canal area ratio (LSAR) from measurements of magnetic resonance imaging (MRI) T2 weighed images. LF from patients with ligamentous stenosis (n=10) were considered as the degenerative hypertrophied samples, and those from patients with non-ligamentous LSS (n=7) and lumbar disc herniation (LDH, n=3) were used as non-hypertrophied controls. Profiling of miRNA from all samples was conducted by Agilent microarray. Microarray data analysis was performed with GeneSpring GX, and pathway analysis was performed using Ingenuity Pathway Analysis.Results: The mean LSAR in the ligamentous group was significantly higher than that in the control group (0.662±0.154 vs 0.301±0.068, p=0.0000171). Ten significantly differentially expressed miRNA were identified and taken as a signature of LF hypertrophy: nine miRNA showed down-regulated expression, and one showed up-regulated expression in the ligamentous LF. Among those, miR-423-5p (rs=-0.473, p<0.05), miR-4306 (rs=-0.628, p<0.01), miR-516b-5p (rs=-0.629, p<0.01), and miR-497-5p (rs=0.461, p<0.05) were correlated to the LSAR. Pathway analysis predicted aryl hydrocarbon receptor signaling (p<0.01), Wnt/β-catenin signaling (p<0.01), and insulin receptor signaling (p<0.05) as canonical pathways associated with the miRNA signature.Conclusions: Classification based on quantification of the MRI axial image is useful for studying hypertrophy of the LF. Aryl hydrocarbon receptor and Wnt/β-catenin signaling may be involved in LF hypertrophy.

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“…Total RNA from plasma and tissues was extracted as previously reported [8]. Input RNA (500 ng) was reverse transcribed to cDNA using a miScript II RT Kit (QIAGEN, Duesseldorf, Germany) according to the manufacturer's instructions.…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

“…However, it remains a challenge to define the major regulators in these processes. We have previously demonstrated a novel potential biomarker, miR-4463, which showed remarkably elevated expression in the plasma of patients with T2DM and patients with T2DM combined with arteriosclerosis obliterans of low extremity arteries (ASO) [8], suggesting that miR-4463 may be involved in the pathogenesis of T2DM and vascular disease. We further discovered that miR-4463 was induced by H 2 O 2 in a concentration-dependent manner, and miR-4463 promotes H 2 O 2 -induced human umbilical vein EC (HUVEC) apoptosis by enhancing oxidative stress and cellular ROS [9].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of MicroRNA-4463 Attenuates High-Glucose- and Hypoxia-Induced Endothelial Cell Injury by Targeting PNUTS

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Vascular complications are the main reasons for disability and mortality associated with type 2 diabetes mellitus (T2DM) and numerous microRNAs (miRNAs) are involved in this process. Our previous study demonstrated that miR-4463 was increased in the plasma of T2DM patients combined with arteriosclerosis of low extremity artery (ASO). However, the role of miR-4463 remains unclear. Methods: miR-4463 expression in the vascular tissues of patients with ASO and T2DM and in human umbilical vein endothelial cells (HUVECs) was detected by qPCR. Cell survival and apoptosis was analyzed via Cell Counting Kit-8 and flow cytometry assays, respectively. Protein expression was determined by Western blot and protein subcellular localization was detected with immunofluorescence. A dual-luciferase assay was used to elucidate the target gene of miR-4463. Results: miR-4463 was elevated in the vascular tissues of patients with T2DM and ASO. In HUVECs, both 25 mmol/L glucose (high glucose, HG) and hypoxia induced miR-4463 expression. Downregulation of miR-4463 promoted HUVEC survival and reduced cell apoptosis under HG and/or hypoxic conditions by facilitating the expression of protein phosphatase-1 nuclear targeting subunit (PNUTS), X-linked inhibitor of apoptosis protein (XIAP), p-AKT, p-Bad, increased the Bcl-2/Bax ratio, as well as downregulated cleaved caspase 3 expression. Mechanistically, we identified PNUTS as a direct target gene of miR-4463. Both the inhibition of AKT phosphorylation and silencing of PNUTS diminished the effect of miR-4463 on HUVEC apoptosis. Moreover, downregulation of miR-4463 enhanced PNUTS to enable PTEN nuclear localization, which resulted in AKT phosphorylation. Conclusion: Our results suggest that downregulation of miR-4463 attenuates cell apoptosis by directly enhancing PNUTS expression to promote PTEN nuclear localization, subsequently activating AKT signaling pathway in HUVECs under HG and/ or hypoxic conditions.

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Altered Plasma MicroRNAs as Novel Biomarkers for Arteriosclerosis Obliterans

Cited by 34 publications

References 41 publications

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

MicroRNA transcriptome analysis on hypertrophy of ligamentum flavum in patients with lumbar spinal stenosis

Downregulation of MicroRNA-4463 Attenuates High-Glucose- and Hypoxia-Induced Endothelial Cell Injury by Targeting PNUTS

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