MicroRNA Profiling in Subventricular Zone after Stroke: MiR-124a Regulates Proliferation of Neural Progenitor Cells through Notch Signaling Pathway

Liu, Xian Shuang; Chopp, Michael; Zhang, Rui Lan; Tang, Tao; Wang, Xin Li; Kassis, Haifa; Hozeska-Solgot, Ann; Zhang, Li; Chen, Charles; Zhang, Zheng Gang

doi:10.1371/journal.pone.0023461

Cited by 194 publications

(164 citation statements)

References 61 publications

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“…Previous studies have demonstrated that let-7 family members are involved in many carcinogenic pathways, including the Notch signaling pathway, which is associated with a number of diseases in humans (29,30). In the present study, hsa-let-7f-1 was found to be downregulated in pneumonia.…”

Section: Discussionsupporting

confidence: 57%

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Huang¹,

Cong²,

Zhai³

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Pneumonia is a lower respiratory tract infection that causes dramatic mortality worldwide. The present study aimed to investigate the pathogenesis of pneumonia and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA from the peripheral blood plasma of participants with pneumonia (severe, n=9; non-severe, n=9) and controls (n=9) was isolated and paired-end sequencing was performed on an Illumina HiSeq4000 system. Following the processing of raw reads, the sequences were aligned against the Genome Reference Consortium human genome assembly 38 reference genome using Bowtie2 software. Reads per kilobase of transcript per million mapped read values were obtained and the limma software package was used to identify differentially expressed miRNAs (DE-miRs). Then, DE-miR targets were predicted and subjected to enrichment analysis. In addition, a protein-protein interaction (PPI) network of the predicted targets was constructed. This analysis identified 11 key DE-miRs in pneumonia samples, including 6 upregulated miRNAs (including hsa-miR-34a and hsa-miR-455) and 5 downregulated miRNAs (including hsa-let-7f-1). All DE-miRs kept their upregulation/downregulation pattern in the control, non-severe pneumonia and severe pneumonia samples. Predicted target genes of DE-miRs in the subjects with non-severe pneumonia vs. the control and the subjects with severe pneumonia vs. the non-severe pneumonia group were markedly enriched in the adherens junction and Wnt signaling pathways. KALRN, Ras homolog family member A (RHOA), β-catenin (CTNNB1), RNA polymerase II subunit K (POLR2K) and amyloid precursor protein (APP) were determined to encode crucial proteins in the PPI network constructed. KALRN was predicted to be a target of hsa-mir-200b, while RHOA, CTNNB1, POLR2K and APP were predicted targets of hsa-let-7f-1. The results of the present study demonstrated that hsa-let-7f-1 may serve a role in the development of cancer and the Notch signaling pathway. Conversely, hsa-miR-455 may be an inhibitor of pneumonia pathogenesis. Furthermore, hsa-miR-200b might promote pneumonia via targeting KALRN.

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Section: Discussionsupporting

confidence: 57%

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Huang¹,

Cong²,

Zhai³

et al. 2017

Experimental and Therapeutic Medicine

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“…20 Thus, if we do not detect the effect of Cerebrolysin on transcription of these genes it would be important to investigate whether Cerebrolysin affects miRNAs. In addition, our laboratory has demonstrated a pivotal role of miRNAs in rats after stroke, 31 and investigation of the effects of Cerebrolysin on miRNA expression may be valuable and provide fundamental insight into mechanisms of therapeutic action.…”

Section: Discussionmentioning

confidence: 99%

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Zhang¹,

Chopp

Meng³

et al. 2013

JNS

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Object Cerebrolysin is a unique peptide preparation that mimics the action of neurotrophic factors. This study was designed to investigate the effects of acute treatment of experimental closed head injury (CHI) in rats with Cerebrolysin on neurological function. Methods Adult male Wistar rats (n = 60) were subjected to impact acceleration–induced CHI. Closed head injured rats received intraperitoneal injection of saline (n = 30) or Cerebrolysin (2.5 ml/kg, n = 30) starting 1 hour postinjury and administered once daily until they were killed (2 or 14 days after CHI). To evaluate functional outcome, the modified neurological severity score (mNSS), foot fault, adhesive removal, and Morris water maze (MWM) tests were performed. Animals were killed on Day 14 (n = 20) after injury, and their brains were removed and processed for measurement of neuronal cells, axonal damage, apoptosis, and neuroblasts. The remaining rats (n = 40) were killed 2 days postinjury to evaluate cerebral microvascular patency by fluorescein isothiocyanate (FITC)–dextran perfusion (n = 16) and to measure the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase–9 (MMP-9) by using real-time reverse transcriptase-polymerase chain reaction (RT-PCR, n = 8) and by immunohistochemical analysis (n = 16). Results At 14 days post-CHI, the Cerebrolysin treatment group exhibited significant improvements in functional outcomes (the adhesive removal, mNSS, foot-fault, and MWM tests), and significantly more neurons and neuroblasts were present in the dentate gyrus (DG) (p < 0.05) compared with the saline-treated group (p < 0.05). At 2 days post-CHI, the Cerebrolysin group exhibited a significantly higher percentage of phosphorylated neurofilament H (pNF-H)–positive staining area in the striatum (p < 0.05), a significant increase in the percentage of FITC-dextran perfused vessels in the brain cortex (p < 0.05), a significant increase in the number of VEGF-positive cells (p < 0.05), and a significant reduction in the MMP-9 staining area (p < 0.05) compared with the saline-treated group. There was no significant difference in mRNA levels of MMP-9 and VEGF in the hippocampus and cortex 48 hours postinjury between Cerebrolysin- and saline-treated rats that sustained CHI. Conclusions Acute Cerebrolysin treatment improves functional recovery in rats after CHI. Cerebrolysin is neuroprotective for CHI (increased neurons in the dentate gyrus and the CA3 regions of the hippocampus and increased neuroblasts in the dentate gyrus) and may preserve axonal integrity in the striatum (significantly increased percentage of pNF-H–positive tissue in the striatum). Reduction of MMP-9 and elevation of VEGF likely contribute to enhancement of vascular patency and integrity as well as neuronal survival induced by Cerebrolysin. These promising results suggest that Cerebrolysin may be a useful treatment in improving the recovery of patients with CHI.

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“…These results demonstrate that miR-181 levels change in response to stroke, and reducing miR-181 protects the brain from stroke by manipulating GRP78. miR-124a is reduced in the subventricular zone neural progenitor cells in vivo (39). In vitro, miR-124a inhibits progenitor cell proliferation and promotes neuronal differentiation by targeting the jagged-Notch signaling pathway.…”

Section: Strokementioning

confidence: 99%

Neuroprotection of microRNA in neurological disorders (Review)

Wang

Cheng

et al. 2014

Biomedical Reports

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Abstract. MicroRNAs (miRNAs) are small, endogenous, non-coding RNA molecules that function as post-transcriptional regulators of gene expression by imperfect base-pairing with the 3'-untranslated regions of their target mRNAs. Altered expression of numerous miRNAs has been shown to be extensively involved in the pathogenesis of various diseases and cancers. Additionally, the specific expression of miRNAs in the nervous system has indicated that miRNAs are critical for the occurrence and development of neurological diseases. Increasing evidence has shown that specific miRNAs target the expression of particular proteins that are significant in the disease pathogenesis. Therefore, miRNA-mediated regulation may be important in the occurrence and development of neurological diseases and may function as a novel biomarker and tool for clinical therapy. In the present study, the significance of miRNAs is reviewed in a number of neurological disorders and the possibility of their use in therapeutic interventions is evaluated.

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MicroRNA Profiling in Subventricular Zone after Stroke: MiR-124a Regulates Proliferation of Neural Progenitor Cells through Notch Signaling Pathway

Cited by 194 publications

References 61 publications

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Neuroprotection of microRNA in neurological disorders (Review)

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