Change in whole-blood microRNA profile during the worsening and recovery process of cerebral infarction, a human study
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE139140 | GEO | 2022/10/10
REPOSITORIES: GEO
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Project description:Indices for diagnosis of hyperacute cerebral infarction (HACI) and prediction of prognosis are essential for timely and appropriate management. MicroRNAs(miRNAs) regulating gene expression following stroke have potential use as prognostic markers of HACI. Here, we explored whether concentrations of circulating miRNAs could be correlated with clinical outcomes and thus form the basis of a system of stroke stratification. Plasma samples from patients with HACI (n = 7) and age-matched healthy volunteers (HVT, n = 4) were screened by microarray to find differentially expressed miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction(qRT-PCR) (HACI:HVT = 33:23). The target genes of the miRNAs with verified differential expression were investigated by GO and KEEG analysis. Using the TOAST (OCSP) criteria and the 3-month modified Rankin Score(mRS), relationships between the expression patterns of specific miRNAs, stroke stratification，and clinical prognosis were determined. The microarray analysis revealed 12 differentially expressed miRNAs. Among seven selected miRNAs verified with qRT-PCR, miR-16 expression in the HACI group was the most significantly different from the HVT group (P < 0.01). Bioinformatics analysis showed that the potential target genes of miR-16 were mainly involved in programmed cell death and the p53 signaling pathways. Receiver operating characteristic(ROC) analysis showed that the area under curve(AUC) of miR-16 was 0.775 (sensitivity 69.7% and specificity 87%) and 0.952 (sensitivity 100% and specificity 91.3%) in overall patients and patients with large artery atherosclerosis (LAAS), respectively. Elevated miR-16 expression was associated with the stroke subtype of LAAS, total anterior circulation infarction, partial anterior circulation infarction, and poor prognosis (P < 0.05). A diagnostic method based on rapid measurement of plasma miR-16 has potential to identify hyperacute cerebral infarction with LAAS with high sensitivity and specificity, which would inform and improve early treatment decisions and disease management.
2016-09-01 | GSE86291 | GEO
Project description:Transplantation of human cranial bone-derived mesenchymal stem cells (hcMSCs) in central nervous system disorders has the potential to improve motor function by highly expressing neurotrophic factors. However, the effects of hcMSCs cultured under microgravity (MG) conditions on cerebral infarction have not been investigated before. Thus, this study aimed to investigate the transplantation effects of hcMSCs cultured in a simulated MG environment on cerebral infarction model rats. Our results showed that neurological function was significantly improved after transplantation of hcMSCs cultured in the MG environment (MG group) compared with normal gravity environment (1G group). Protein expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the MG group than in the IG group, whereas sortilin 1 expression was significantly lower. MicroRNA analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, anti-apoptosis, neural and synaptic organization, and cell differentiation inhibition were significantly upregulated in the MG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results indicate that hcMSCs cultured in an MG environment may be a useful source of stem cells for recovery of neurological function after cerebral infarction.
2023-12-17 | GSE250211 | GEO
Project description:Umbilical cord blood (UCB) transplantation shows pro-angiogenic effect and contributes to symptom amelioration in animal models of cerebral infarction. OP9 is a stromal cell line used as feeder cells to promote hematoendothelial differentiation of embryonic stem cells. We co-cultured UCB 24hr with OP9 (i.e. OP9 preconditioning) and investigated its change in angiogenic properties and underlying mechanisms. Single cell RNA sequencing showed prominent phenotypic shift toward M2 in monocytic fraction of OP9 pre-conditioned UCB.
2023-01-25 | GSE207249 | GEO
Project description:How the complex interaction between Mycobacterium tuberculosis (Mtb) and the host is regulated during infection is still not well understood. Using a systems biology approach, we demonstrate here that miR-155 is one of several microRNAs that regulate host gene expression over the first 48 hours of Mtb infection in macrophages. miR-155 regulates the cell survival of Mtb-infected macrophages through SHIP1/AKT signaling. Using timecourse gene expression data, we constructed a miRNA regulatory network for the innate immune response to Mtb infection by WT macrophages. The network suggested a role for seven miRNAs in regulating the host response to Mtb, with miR-155 being one of them. We then validated a role for miR-155 by comparing the response between WT and miR-155-/- macrophages.
2016-09-14 | GSE79731 | GEO
Project description:How the complex interaction between Mycobacterium tuberculosis (Mtb) and the host is regulated during infection is still not well understood. Using a systems biology approach, we demonstrate here that miR-155 is one of several microRNAs that regulate host gene expression over the first 48 hours of Mtb infection in macrophages. miR-155 regulates the cell survival of Mtb-infected macrophages through SHIP1/AKT signaling. Using timecourse gene expression data, we constructed a miRNA regulatory network for the innate immune response to Mtb infection by WT macrophages. The network suggested a role for seven miRNAs in regulating the host response to Mtb, with miR-155 being one of them. We then validated a role for miR-155 by comparing the response between WT and miR-155-/- macrophages.
2016-09-14 | GSE79732 | GEO
Project description:microRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3’ untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA—miR-155—in a genetically controlled manner. We found that approximately forty percent of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these non-canonical sites feature extensive complementarity to the miRNA seed with one mismatch. These non-canonical sites confer regulation of gene expression albeit less potently than canonical sites. Thus, non-canonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation. We used microarrays to measure changes in gene expression between activated wild type (WT) and miR-155 deficient (155KO) primary CD4 T cells.
2012-11-09 | GSE41241 | GEO
Project description:Purpose: We compared the levels of miRNA specific for DEGs in isograft corneas with those in normal corneas, as well as the levels of miRNA specific for DEGs in allograft corneas with those in isograft corneas, to gain a better understanding of molecular variables that affect corneal graft rejection pathways. Methods: Illumina Hiseq 2500 deep sequencing was used to screen for differentially expressed genes (DEGs) in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Potential target genes among the DEGs were predicted using target prediction software (TargetScan, Miranda, miRDB, and CLIP), and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis. Results: Our results showed that 22 miRNAs were significantly upregulated and 4 were significantly downregulated in the isograft group when compared with the control group (P < 0.01), while 17 miRNAs were significantly upregulated and 3 were significantly downregulated in the allograft group when compared with the isograft group (P < 0.01). Among the miRNAs with altered expression levels, miR-155-5p, miR-142-3p, miR-142-5p, and miR-223-3p displayed simultaneous changes in the above two comparisons. Potential target genes among the DEGs were predicted using target prediction software, and the overlay portion was analyzed using the Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). GO and KEGG analyses showed that the DEGs were mainly involved in metabolic pathways, cytokine secretion, and tumor immunity functions. An analysis of the interactions between DEG proteins (PPI analysis) and a MetaCore software analysis of 4 key DEGs revealed that the genes regulated by miR-155-5p played important roles in the miRNA-mRNA regulatory network. Furthermore, the MetaCore analysis identified C/EBP beta, p53, and sp1 as key transcription factors in that network. Conclusions: Our study identified transplanted corneas-specific miRNA in matched pairs of isograft corneas and normal corneas, allograft corneas and isograft corneas. Furthermore, bioinformatics analysis of the key miRNA regulatory network revealed the molecular mechanisms, which suggests miRNAs may as new molecular targets for treating corneal injuries and corneal transplant rejection
2018-04-28 | GSE113787 | GEO
Project description:microRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3’ untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA—miR-155—in a genetically controlled manner. We found that approximately forty percent of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these non-canonical sites feature extensive complementarity to the miRNA seed with one mismatch. These non-canonical sites confer regulation of gene expression albeit less potently than canonical sites. Thus, non-canonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation. We used microarrays to measure changes in gene expression between activated wild type (WT) and miR-155 deficient (155KO) primary CD4 T cells. CD4 T cells were harvested from WT and miR-155 KO mice (Thai et al., 2007) and activated for 3 days in vitro. Each array is from a separate biological replicate, which are cells originating from a separate mouse.
2012-11-09 | E-GEOD-41241 | biostudies-arrayexpress
Project description:Huntington’s disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level but the maximum tolerable dose and long-term effects of such a treatment are unknown. Using a self-complementary AAV9 vector, we delivered a mir-155 based artificial miRNA under the control of the chicken ß-actin or human U6 promoter. In mouse brain, the artificial miRNA reduced the human huntingtin mRNA by 50%. The U6, but not the CßA promoter, produced the artificial miRNA at supraphysiologic levels. Embedding the antisense strand in a U6-mir-30 scaffold reduced expression of the antisense strand but increased the sense strand. In mice treated with scAAV9-U6-mir-155-HTT or scAAV9-CßA-mir-155-HTT, activated microglia were present around the injection site one-month post-injection. Six-months post-injection, mice treated with scAAV9-CßA-mir-155-HTT were indistinguishable from controls. Those that received scAAV9-U6-mir-155-HTT showed behavioural abnormalities and striatal damage. In conclusion, miRNA backbone and promoter can be used together to modulate expression levels and strand selection of artificial miRNAs and in brain the CßA promoter can provide an effective and safe dose of a human huntingtin. We also performed RNAseq on total RNA. In the mice injected with AAV9-U6-anti-HTT-6433, 44 transcripts were significantly downregulated while 30 were significantly upregulated when compared to the naïve control. In the AAV-CßA-anti-HTT-6433 group, 12 transcripts were downregulated and 4 were upregulated. Overall, transcripts containing a seed sequence target are downregulated in the scAAV-U6-anti-HTT-6433 group but not the scAAV9-CßA-anti-HTT-6433 group.
2017-04-24 | GSE97353 | GEO