Profiling of circRNA Expression in Human Ovarian Clear Cell Carcinoma (OCCC)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE266248 | GEO | 2024/05/17
REPOSITORIES: GEO
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Project description:Circular RNAs (circRNAs), a noncoding RNA class originating from alternative splicing, are highly abundant in neural tissues and were shown to regulate gene expression e.g. by interacting with microRNAs and RNA-binding proteins. Neuroblastoma is an embryonal neoplasia, which arises from undifferentiated neural crest cells. Here, we aimed to explore, whether circRNAs influence the pathogenesis of high-risk neuroblastoma. We performed whole-transcriptome sequencing of 104 primary neuroblastoma samples of all risk-groups and identified 5,203 unique circRNAs involving 2,302 genes. Candidate circRNA expression did not correlate with host gene expression, indicating independent regulatory mechanisms. circRNAs were significantly downregulated in the MYCN-amplified high-risk tumors. These findings were independently reproduced in a tetracycline-inducible MYCN-overexpression system based on a non MYCN-amplified neuroblastoma cell line, suggesting that MYCN drives this global circRNA repression. We identified the RNA helicase DHX9 as a mediator of this global suppressive effect of MYCN on circRNAs. Comparing our RNA sequencing data with other cancers and controls revealed a circRNA subset specifically upregulated in neuroblastoma that included a circRNA derived from the ARID1A tumor suppressor gene. Specific circARID1A knockdown resulted in reduced proliferation, cell numbers and viability, prompted apoptosis and induced a differentiated phenotype. Neither knockdown, nor overexpression of circARID1A influenced ARID1A mRNA and protein levels significantly. To dissect the potential mode of function, we performed a pulldown assay with subsequent mass spectrometry. We identified the RNA-binding protein KHSRP as an interaction partner that participates in the mechanism of action of circARID1A. In summary, this study highlights an important role of circRNAs in neuroblastoma biology and may establish this RNA class as a future therapeutic target and biomarker.
2023-04-06 | PXD026053 | Pride
Project description:Punch biopsies from patients with BCC (n=3) and non-lesional skin (n=3) were included in the study. Microarray based circRNA expression profiles were acquired using Arraystar circRNA Arrays V. 2.0 screening for 13,617 distinct human circRNA candidates. We identified circRNAs differentially expressed in BCC compared to non-lesional skin (control).
2016-04-21 | GSE74756 | GEO
Project description:Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents an immunopeptidomics workflow with a specific focus on generating a circRNA-specific protein fasta reference. The main goal of this workflow is to streamline the process of identifying and validating human leukocyte antigen (HLA) bound peptides potentially originating from circRNAs. We increased the analytical stringency of our workflow by retaining peptides identified independently by two mass spectrometry search engines and/or by applying a group-specific FDR for canonical-derived and circRNA-derived peptides. A subset of circRNA-derived peptides specifically encoded by the region spanning the back-splice junction (BSJ) were validated with targeted MS, and with direct Sanger sequencing of the respective source transcripts. Our workflow identified 54 unique BSJ-spanning circRNA-derived peptides in the immunopeptidome of melanoma and lung cancer samples. Our novel approach enlarges the catalog of source proteins that can be explored for immunotherapy.
2024-03-20 | PXD043989 | Pride
Project description:Profiling of circRNA Expression in Human Ovarian Clear Cell Carcinoma (OCCC)
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Project description:The diversity of chemoresistant OCCC is unknown. We performed single nucleus RNA sequencing (snRNA-seq) to analyze the diversity of OCCC.
2024-03-30 | GSE224334 | GEO
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:Arraystar Human circRNA Microarray is designed for the global profiling of human circRNAs. In this study, we applied a circRNA microarray to screen the potential biomarker for HCC. 20 samples extracted from plasma samples including HCC group before operation, and after operation, CH group and control group. Each group contained five samples.
2021-03-02 | E-MTAB-8799 | biostudies-arrayexpress
Project description:Circular RNAs are a class of non-coding RNAs mostly generated by back-splicing RNA transcripts of protein-coding gene loci. In difference to canoncial splicing, back-splicing ligates downstream splice donor site with an upstream splice acceptor generating a covalently closed circular RNA. CircRNAs have been reported to influence cellular functions by acting as miRNA sponges, regulation of host gene transcription or by protein interactions. The circRNA cZNF292 has been previously reported to be regulated under hypoxia and to influence endothelial cell angiogenesis and functions. The present data set aims to identfy protein interactions partners of cZNF292 in endothelial cells to further characterize the mechanism of action of cZNF292. Dataset comprises 8 replicates of proteins identified after biotin-based 2'O-Me RNA antisense affinity purification of the circRNA cZNF292 from HUVEC (human umbilical vein endothelial cell) lysates compared to a control probe dataset. Purification was performed without cross-linking under low salt and mild detergent conditions.
2022-11-29 | PXD029794 | Pride
Project description:Circular RNA expression profiling of human nucleus pulposus derived from patients with IDD in comparison with those derived from cadaveric disc as normal control. We have identified the expression profiles of miRNAs (GSE63492), lncRNAs, mRNAs (GSE56081) in IDD using 5 normal discs as control and 5 IDD discs. Accumulating evidence indicates that circRNAs are key regulators of gene expression by interacting with miRNAs. circRNA is a novel type of RNA that, unlike linear RNA, forms a covalently closed continuous loop, and is highly represented in the eukaryotic transcriptome. Two-condition experiment: control nucleus pulposus vs. degenerative nucleus pulposus. Biological replicates: 5 control, 5 degenerated, independently harvested (the same samples as GSE56081 and GSE63492). Four replicates per array.
2016-08-04 | E-GEOD-67566 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Examination of 12 samples in different stages of C.elegans development.
2015-01-06 | E-GEOD-63823 | biostudies-arrayexpress