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

Analysis of circRNA,mRNA and miRNA in depolarized neuroblastoma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-03-06 | GSE139443 | GEO

Environmental cadmium-induced circRNA-miRNA-mRNA network regulatory mechanism in human normal liver cell model [circRNA]

Project description:Cadmium is a naturally existing heavy metal and a typical environmental pollutant which is a significant threat to human health and can lead to acute and chronic damage to various organs. At present, hundreds of lncRNAs and miRNAs have been confirmed to be related to the toxicity of Cd. However, the role of circRNA in the toxicity of Cd and the involved regulatory mechanism has not been clarified. In this work, human normal liver cell (L-02) was selected as model to identify the changes in the expression level of circRNA after exposure to Cd. Total RNA of each sample was extracted by Trizol method, the original data of circRNA, miRNA and mRNA expression levels of each sample were obtained by microarray hybridization and scanning were standardized and differentially expressed. Differential circRNAs, miRNAs, and mRNAs associated with the toxic effects of Cd were identified. Construct a ceRNA network by screening the predicted circRNA, miRNA and mRNA and predict the main biological functions and metabolic pathways of the network. A total of 266 different circRNAs, 223 different miRNAs and 519 different mRNAs were identified by differential expression analysis. After screening, seven circRNAs, 10 miRNAs and 97 mRNAs were constructed into ceRNA network. After GO enrichment and KEGG pathway analysis of 97 mRNAs in circRNA-miRNA-mRNA network, indicated that circRNA in the ceRNA network may regulate cell proliferation, apoptosis, oxidative stress and inflammatory response under the toxic effect of Cd to damage L-02, and it has obvious dose-response effect and time effect.

2024-10-08 | GSE246129 | GEO

Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks [circRNA]

Project description:Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks [circRNA]

| PRJNA884697 | ENA

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