Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6977090_1.fastq.gz | Fastqsanger.gz | |||
| SRR6977090_2.fastq.gz | Fastqsanger.gz | |||
| SRR6977091_1.fastq.gz | Fastqsanger.gz | |||
| SRR6977091_2.fastq.gz | Fastqsanger.gz | |||
| SRR6977092_1.fastq.gz | Fastqsanger.gz |
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Project description:Receptor tyrosine kinase pathway signalings plays a central role in the growth and progression of glioblastoma, a highly aggressive group of brain tumors. We recently reported that miR-218 repression, an essentially uniform feature of human GBM, directly promotes RTK hyperactivation by increasing the expression of key positive signaling effectors, including EGFR, PLCr1, PIK3CA and ARAF. However, enhanced RTK signaling is known to activate compensatory inhibitory feedback mechanisms in both normal and cancer cells. We demonstrate here that miR-218 repression in GBM cells also increases the abundance of additional up stream and downstream signaling mediators, including PDGFRa, RSK2, and S6K1, which collectively funciton to alleviate inhibitory RTK feedback regulation. In turn, RTK signaling suppresses miR-218 expression via STAT3, which binds to the miR-218 locus, along with BCLAF1, to repress its expression. These data identify novel interacting feedback loops by which miR-218 repression promotes increased RTK signaling in high-grade gliomas.
2022-03-01 | PXD002112 | Pride
Project description:Motor-neuron specific microRNA-218 (miR-218) was recently put in the spotlight because of its striking roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons miR-218 is downregulated and its mRNA targets are reciprocally upregulated (de-repressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. Intriguingly, miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity uncovers a previously unappreciated facet of motor neuron specificity that may be particularly susceptible to failure in human ALS, contributes to a view of ALS as a disease with a prominent RNA component and suggests that miR-218 is a potential therapeutic target for motor neuron disease.
2019-08-28 | GSE136409 | GEO
Project description:Objective: Fibroblast-like synovial cells (FLS) have multilineage differentiation potential including osteoblasts. We aimed to investigate the role of microRNAs during the osteogenic differentiation of rheumatoid arthritis (RA)-FLS. Methods: MicroRNA(miRNA) array analysis was performed to investigate the differentially expressed miRNAs during the osteogenic differentiation. Expression of miR-218-5p (miR-218) during the osteogenic differentiation was determined by quantitative real-time PCR. Transfection with miR-218 precursor and inhibitor were used to confirm the targets of miR-218 and to analyse the ability of miR-218 to induce osteogenic differentiation. Results: The miRNA array revealed that 12 miRNAs were up-regulated and 24 miRNAs were down-regulated after osteogenic differentiation. We observed that miR-218 rose in the early phase of osteogenic differentiation and then decreased. Micro array analysis revealed the mir-218 modulate the expression of ROBO1 in RA-FLS. The induction of miR-218 in RA-FLS decreased ROBO1 expression, and promoted osteogenic differentiation.
2018-03-26 | GSE111946 | GEO
Project description:Noncoding RNAs, especially microRNAs (miRNAs) have been implicated in the regulation of neuronal functions, such as learning, cognition and memory formation. However, the particular miRNAs involved in drug-induced behavioral plasticity are largely unknown. Here we report a novel regulator, miR-218, that inhibits heroin-induced behavioral plasticity. Network propagation-based method revealed several miRNAs that play key roles in drug-addiction, among which, miR-218 was decreased in nucleus accumbens (NAc) after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioning place preference (CPP) test and heroin self-administration (SA) experiment. Luciferase activity assay indicated miR-218 could regulate neuroplasticity related genes and directly target Mecp2 3’UTR. Consistently, Mecp2-/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, Mecp2, in the regulation of heroin-induced behavioral plasticity.
2017-03-08 | GSE89202 | GEO
Project description:The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. Post-transcriptional regulation of gene expression by microRNAs (miRNAs) is a key aspect of this program. Indeed, deletion of neuron-enriched miRNAs induces strong developmental phenotypes, and miRNA levels are altered in patients with neurodevelopmental disorders. However, the mechanisms used by miRNAs to instruct brain development remain largely unexplored. Here, we identified miR-218 as a critical regulator of hippocampal assembly. MiR-218 is highly expressed in the hippocampus and enriched in both excitatory principal neurons (PNs) and GABAergic inhibitory interneurons (INs). Early life inhibition of miR-218 results in an adult brain with a predisposition to seizures. Changes in gene expression in the absence of miR-218 suggest that network assembly is impaired. Indeed, we find that miR-218 inhibition results in the disruption of early depolarizing GABAergic signaling, structural defects in dendritic spines, and altered intrinsic membrane excitability. Conditional knockout of miR-218 in INs, but not PNs, is sufficient to recapitulate long-term instability. Finally, de-repressing Kif21b and Syt13, two miR-218 targets, phenocopies the effects on early synchronous network activity induced by miR-218 inhibition. Taken together, the data suggest that miR-218 orchestrates formative events in PNs and INs to produce stable networks.
2023-10-15 | GSE241245 | GEO
Project description:Lung cancer is the leading cause of cancer death worldwide. Brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker in epithelial-mesenchymal transition) and ADAM9 (a member of type I transmembrane proteins) have been reported relating to lung cancer brain metastasis, however, it is still not clear whether any interaction between them to mediate lung cancer brain metastasis. Since microRNAs were discovered to regulate many biological functions and disease processes (e.g., cancer) by down-regulating their target genes, microRNA microarrays were used to identify ADAM9 regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and immunoblotting proved that CDH2 was a target gene of miR-218. The expression of miR-218 was generated from pri-mir-218-1, located in SLIT2, in low invasive lung adenocarcinoma while it was inhibited in aggressive lung adenocarcinoma. Down-regulation of ADAM9 could up-regulate SLIT2 and miR-218, thus down-regulate CDH2 expression. This study elucidated the mechanism of ADAM9 activating CDH2 may be due to release the inhibition of miR-218 on CDH2 in lung adenocarcinoma.
2016-01-01 | GSE51833 | GEO
Project description:To investigate differences in gene expression after overexpression miR-218 in U251MG 2 Samples, one transduced with miR-control and one with miR-218.
2013-04-19 | E-GEOD-46059 | biostudies-arrayexpress
Project description:miRNAs are post-transcriptional repressors with wide variation in cellular abundance across cell types and disease states. Yet, the transcriptomic and biological impact of altering miRNA levels (rather than binary gain or loss) has not been systematically investigated. By genetic combination, we generated an allelic series of mice expressing varying levels of miR-218, a motor neuron-specific miRNA associated with amyotrophic lateral sclerosis (ALS). Modulation of miR-218 dose causes threshold-like neuromuscular synaptogenesis and mouse viability phenotypes and revealed heterogenous dose-response curves of target mRNA repression. A dose-response network analyses unmasked a specific regulon exhibiting an inflection point in repression concomitant with the emergence of motor phenotypes. Furthermore, we find that miR-218 indirectly activates a coherent peripheral neuronal genetic signature and that the magnitude of miR-218 mediated effects varies in distinct motor subpopulations. This work reveals miRNA dose as a potent, non-linear modulator of in vivo mRNA target selection, suggesting how cellular dysfunction might abruptly arise when miRNA levels fall below a critical threshold. For the data uploaded here, motor neurons carrying an Hb9:gfp reporter were FACS isolated based upon GFP expression and used for either bulk or single cell RNA sequencing (10x genomics). Motor neurons were either mouse embryonic stem cell derived motor neurons (ESMNs) or mouse motor neurons from developmental stage E12. ESMN samples carry unique mutations of the miR-218-2 promoter of distinct sizes, or are wild type. E12 motor neurons carry combinations of mutations to either miR-218-1 or miR-218-2 or the promoter for miR-218-2. For single cell RNA sequencing, we have WT and miR-218 double knockout (DKO) motor neurons in duplicate. We also sequenced 4 samples of dorsal root ganglia from E12 mice (DRG1-4).
2021-08-27 | E-MTAB-10571 | biostudies-arrayexpress
Project description:We investigated microRNA expression in motoneurons by performing small RNA sequencing of fluorescence-activated cell sorting (FACS)-isolated motoneurons labelled with the Hb9:gfp transgenic reporter and Hb9:gfp negative non-motoneurons including spinal interneurons. We find that one microRNA, microRNA-218, is highly enriched and abundantly expressed in motoneurons. Furthermore, we find that miR-218 is transcribed from alternative, motoneuron-specific alternative promoters embedded within the Slit2 and Slit3 genes by performing RNA sequencing of FACS-isolated motoneurons and a dissected embryonic floor plate cells which served as a control. Next, we performed RNA sequencing of FACS-isolated wild type (WT) motoneurons and motoneurons lacking miR-218 expression (218DKO motoneurons), and find that a large set of genes (named 'TARGET218' genes) with predicted miR-218 binding sites are de-repressed in the absence of miR-218 expression. Finally, we examine the expression of TARGET218 genes in other neuronal subpopulations by FACS-isolating V1, V2a, and V3 interneurons expressing Cre-inducible fluorescent reporters and performing RNA sequencing. We find that the TARGET218 network of genes is depleted in wild-type motoneurons versus these interneuron types. Additionally, these genes are expressed at similar levels in 218DKO motoneurons compared with interneuron subtypes, suggesting that this genetic network.
2015-12-18 | GSE75600 | GEO
Project description:The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play an important role in regulating OSCC invasion. In this study, we modeled the OSCC invasion front on a microfluidic chip and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing and bioinformatic analysis. We found that miR-218-5p was downregulated in invasion front cells; a luciferase reporter assay confirmed that cluster of differentiation (CD)44 was a direct target of miR-218-5p. Inhibiting miR-218-5p in invasion front cells activated CD44- Rho-associated protein kinase (ROCK) signaling and promoted cell invasion by inducing cytoskeletal reorganization. These findings indicate that miR-218-5p negatively regulates OSCC invasiveness by targeting the CD44–ROCK pathway and may be a useful therapeutic target for OSCC. Moreover, our method of modeling and isolating invasion front cells using a microfluidic chip is a time-saving alternative to in vivo models.
2018-05-21 | GSE107243 | GEO