Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-Beta pathway
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ABSTRACT:
PROVIDER: PRJNA437858 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6825140.fastq.gz | Fastqsanger.gz | |||
| SRR6825131.fastq.gz | Fastqsanger.gz | |||
| SRR6825141.fastq.gz | Fastqsanger.gz | |||
| SRR6825132.fastq.gz | Fastqsanger.gz | |||
| SRR6825142.fastq.gz | Fastqsanger.gz |
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Project description:Rationale: Competitive endogenous RNA (ceRNA) networks play important roles in posttranscriptional regulation. Their dysregulation is common in cancer. However, ceRNA signatures have been poorly examined in the invasive and aggressive phenotypes of mesenchymal glioblastoma (GBM). This study aims to characterize mesenchymal glioblastoma at the mRNA-miRNA level and identify the mRNAs in ceRNA networks (micNET) markers and their mechanisms in tumorigenesis. Methods: The mRNAs in ceRNA networks (micNETs) of glioblastoma were investigated by constructing a GBM ceRNA network followed by integration with a STRING protein interaction network. The prognostic micNET markers of mesenchymal GBM were identified and validated across multiple datasets. ceRNA interactions were identified between micNETs and miR181 family members. LY2109761, an inhibitor of TGFBR2, demonstrated tumor-suppressive effects on both primary cultured cells and a patient-derived xenograft intracranial model. Results: We characterized mesenchymal glioblastoma at the mRNA-miRNA level and reported a ceRNA network that could separate the mesenchymal subtype from other subtypes. Six genes (TGFBR2, RUNX1, PPARG, ACSL1, GIT2 and RAP1B) that interacted with each other in both a ceRNA-related manner and in terms of their protein functions were identified as markers of the mesenchymal subtype. The coding sequence (CDS) and 3'-untranslated region (UTR) of TGFBR2 upregulated the expression of these genes, whereas TGFBR2 inhibition by siRNA or miR-181a/d suppressed their expression levels. Furthermore, mesenchymal subtype-related genes and the invasion phenotype could be reversed by suppressing the six mesenchymal marker genes. Conclusions: This study suggests that the micNETs may have translational significance in the diagnosis of mesenchymal GBM and may be novel therapeutic targets.
| S-EPMC6160778 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-07 | GSE111676 | GEO
Project description:Expression changes of competitive endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts that contain miRNA binding sites. Here, we find that although miRNA levels define the extent of repression, they do not affect the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ~20% of that observed for canonical 8-nt sites. Sites with extensive additional complementarity can be even more potent, but this occurs predominantly through miRNA degradation rather than competition. Cooperative binding of closely spaced sites for different miRNAs can also increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNA and target abundance, target-site spacing and affinity requirements for ceRNA-mediated gene regulation and specify the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Sixty-four mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing sites matching miR-122, let-7, miR-192, miR-194 or a mutated site (no site) or 2) embryonic stem (ES) cells that were transfected with a Tet-inducible dual-color reporter construct expressing enhanced yellow fluorescent protein (eYFP) and mCherry that contains zero (0s) or three (3s) 8 nt miRNA seed matches for miR-293 or miR-92 in the 3� UTR. ES cells were sorted with a FACSAria IIIu flow cytometer into three bins based on their eYFP fluorescence intensity. All samples were sequenced in duplicates by an Illumina HiSeq 2500. Library preparation and sequencing were performed by Fasteris SA (Switzerland) or by the Functional Genomics Centre Zürich (FGCZ). Three small RNA profiles or either primary hepatocytes or embryonic stem cells were also generated by Solexa sequencing.
2016-10-27 | E-GEOD-76288 | biostudies-arrayexpress
Project description:Human MRC5 pulmonary fibroblasts (CCL-171) were exposed or not to TGF-β at 10 ng/mL. RNA samples were harvested 24 hours after TGF-β exposition. Two independent experiments were carried out.
2019-04-11 | GSE97833 | GEO
Project description:TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma. Differential gene expression analysis of patient-derived primary cultured glioblastoma cells treated with the TGF-beta receptor inhibitor, LY2109761
2011-01-27 | GSE23935 | GEO
Project description:TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma. Differential gene expression analysis of patient-derived primary cultured glioblastoma cells treated with the TGF-beta receptor inhibitor, LY2109761 11 patient-derived cell cultures from 11 patients were treated with 2microM of the TGF-beta receptor inhibitor, LY2109761, for 3 hours or left untreated and RNA was isolated and microarray analysis was performed
2011-01-27 | E-GEOD-23935 | biostudies-arrayexpress
Project description:Background and objectiveIntervertebral disc degeneration (IDD) is a complex multifactorial and irreversible pathological process. In IDD, multiple competing endogenous RNAs (ceRNA, including mRNA, lncRNA, and pseudogenes) can compete to bind with miRNAs. However, the potential metabolic signatures in nucleus pulposus (NP) cells remain poorly understood. This study investigated key metabolic genes and the ceRNA regulatory mechanisms in the pathogenesis of IDD based on microarray datasets.MethodsWe retrieved and downloaded four independent IDD microarray datasets from the Gene Expression Omnibus. Combining the predicted interactions from online databases (miRcode, miRDB, miRTarBase, and TargetScan), differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified. A ceRNA network was constructed and annotated using GO and KEGG pathway enrichment analyses. Moreover, we searched the online metabolic gene set and used support vector machine (SVM) to find the critical metabolic DEmRNA(s) and other DERNAs. Differential gene expression was validated with a merged dataset.ResultsA total of 45 DEmRNAs, 36 DElncRNAs, and only one DEmiRNA (miR-338-3p) were identified in the IDD microarray datasets. GO and KEGG pathway enrichment analyses revealed that the DEmRNAs were predominantly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, apoptosis, and cellular response to oxidative stress. Based on SVM screening, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK/FBPase) 2 is the critical metabolic gene with lower expression in IDD, and AC063977.6 is the key lncRNA with lower expression in IDD. The ceRNA hypothesis suggests that AC063977.6, miR-338-3p (high expression), and PFKFB2 are dysregulated as an axis in IDD.ConclusionsThe results suggest that lncRNA AC063977.6 correlate with PFKFB2, the vital metabolic signature gene, via targeting miR-338-3p during IDD pathogenesis. The current study may shed light on unraveling the pathogenesis of IDD.
| S-EPMC7937257 | biostudies-literature
Project description:Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a miRNA through their binding sites and that changes in ceRNA abundances from individual genes can modulate the miRNA’s activity. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target-site abundance through expression of a miR-122 target in hepatocytes and livers, and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target-site abundance (≥1.5x10^5 added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target-site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect. Seventeen mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing either 1 or 3 sites matching miR-122 or a mutated miR-122 site (no site), 2) primary hepatocytes derived from mice treated with Antagomir-122 (treatment group) or Antagomir-122mm (control group), 3) livers originating of a genetic model (Ldlr deficient mice) causing severe pathological changes in cholesterol metabolism, 4) livers of mice perfused with Insulin or PBS, and 5) livers of mice fed a high-fat or chow diet; most samples were sequenced in duplicate or triplicate by an Illumina HiSeq 2000. One small RNA profile was also generated from livers of mice fed a chow diet by Solexa sequencing.
2014-05-01 | E-GEOD-52801 | biostudies-arrayexpress
Project description:Failure of human rhombic lip differentiation constitutes medulloblastoma
| PRJNA826820 | ENA