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

Human circRNA expression profiling in plasma sample of hepatocellular carcinoma

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

Identification of circRNA-interacting proteins in pancreatic ductal adenocarcinoma

Project description:Many studies have demonstrated the importance of circRNA in regulating gene expression through functioning as microRNA sponges. However, the roles of circRNA-protein interaction are not fully understood. Importantly, how circRNA-protein interaction contributes the progression of pancreatic ductal adenocarcinoma is largely unexplored. Therefore, RNA Pull down assay for investigating RNA-protein interaction was performed in PANC-1 cells.

2022-02-15 | PXD015048 | Pride

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