Circular RNAs upregulated in medulloblastoma regulate proliferation and growth of tumor cells via host genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101739 | GEO | 2020/07/21
REPOSITORIES: GEO
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Project description:Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Detection of circRNAs from RNA-Seq â triplicate
2015-12-17 | E-GEOD-71195 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Histone 3 Lysine 27 Acetylation â 2 replicates
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Project description:To explore the potential involvement of circular RNAs (circRNAs) in pancreatic ductal adenocarcinoma (PDAC) oncogenesis, we conducted circRNA profiling in six pairs of human PDAC and adjacent normal tissue by microarray. Our results showed that clusters of circRNAs were aberrantly expressed in PDAC compared with normal samples, and provided potential targets for future treatment of PDAC and novel insights into PDAC biology. Analyze circular RNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform.
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Project description:Circular RNAs (circRNAs), formed by the atypical head-to-tail splicing of exons, have re-emerged as a potentially interesting RNA species given recent reports of a surprising diversity and abundance of circRNA in organisms ranging from worm to human. Here, using deep RNA sequencing, we profiled different RNA species in mouse and observed that circRNAs are significantly enriched in neural tissue, relative to other tissues. Using PacBio sequencing, we determined, for the first time, the circular structure of this population of circRNAs as well as their full-length sequences. We discovered that a disproportionate fraction of the brain circRNA population is derived from host genes that code for synaptic proteins. Moreover, based on the separate profiling of the RNAs localized in neuronal cell bodies and neuropil (enriched in axons and dendrites), we found that, on average, circular RNAs are more enriched in the neuropil than their host gene mRNA isoforms. Using high resolution in situ hybridization we, for the first time, directly visualized circRNA punctae in the dendrites of neurons. The host gene origin and location of the circRNA in neurons suggest the possibility that circRNAs might participate in the regulation of synaptic function and plasticity. Consistent with this idea, we observed via profiling at different developmental stages, that the abundance of many circular RNAs changes abruptly at a time corresponding to synaptogenesis. In addition, following a homeostatic downscaling of neuronal activity many circRNAs exhibit significant up or down-regulation. These data indicate that brain circRNAs are positioned to respond to and regulate synaptic function. Circular RNA profiling in 13 different samples in mice and four samples in rat, using Illumina sequencing
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Project description:The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type–specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their flanking linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a primate-specific zinc-finger gene, ZNF91. These results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs. Examination of 9 samples in 1 cell type Note: The ENCODE data we used are under GEO SuperSeries GSE26284 (all samples labeled "_cell_total"). But they were not used in the processing of the U2OS data.
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Project description:To test the hypothesis that circRNAs might encode functional peptides in mammalian cells, we studied the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT), which was previously reported as a tumor suppressor and connected p53 activation with polycomb repressive complex 2 (PRC2). We selected this long noncoding RNA (lncRNA) for further analysis because LINC-PINT has a long exon 2 which in accordance with the bioinformatical analyzed circular RNA standard.The following immunoblotting showed 87aa peptide level also decreased, indicating that this peptide is encoded by circPINTexon2. We name this circRNA encoded peptide PINT87aa. To investigate the possible regulatory role of PINT87aa, we did the expression micro array in PINT87aa stably transfect U251 or U87 glioblastoma cells and their control cells. The array analysis reveals that PINT87aa may involve in the cell cycle regulation, anti-apoptosis effects and multiple oncogenic signaling pathway activation.
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Project description:Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. Sequencing of blood RNA from five healthy individuals (biological replicates) plus technical replicate of one sample and detection of circRNAs.
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