PXD026053

PXD026053 is an original dataset announced via ProteomeXchange.

Title	human circRNA binding proteins in neuroblastoma
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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:04.013.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-17 05:49:02	ID requested
1	2023-04-06 08:42:05	announced
2	2023-07-12 03:04:28	announced	2023-07-12: Updated project metadata.
⏵ 3	2023-11-14 09:02:04	announced	2023-11-14: Updated project metadata.

Fuchs S, Dan, ß, mann C, Klironomos F, Winkler A, Fallmann J, Kruetzfeldt LM, Szymansky A, Naderi J, Bernhart SH, Grunewald L, Helmsauer K, Rodriguez-Fos E, Kirchner M, Mertins P, Astrahantseff K, Suenkel C, Toedling J, Meggetto F, Remke M, Stadler PF, Hundsdoerfer P, Deubzer HE, K, ü, nkele A, Lang P, Fuchs J, Henssen AG, Eggert A, Rajewsky N, Hertwig F, Schulte JH, Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN. Nat Commun, 14(1):3936(2023) [pubmed]

submitter keyword: Human, Neuroblastoma, IMR-5, LC-MS

Philipp Mertins
contact affiliation	Proteomics Unit, BIH@Charite, Robert Roessle Strasse 10, 13125 Berlin, Germany
contact email	philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD026053

PRIDE project URI

• PRIDE
  1. PXD026053
     1. Label: PRIDE project
     2. Name: human circRNA binding proteins in neuroblastoma