dc.contributor.author
Malhan, Deeksha
dc.contributor.author
Basti, Alireza
dc.contributor.author
Relógio, Angela
dc.date.accessioned
2024-02-15T12:39:11Z
dc.date.available
2024-02-15T12:39:11Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/42433
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-42157
dc.description.abstract
Emerging evidence points towards a regulatory role of the circadian clock in alternative splicing (AS). Whether alterations in core-clock components may contribute to differential AS events is largely unknown. To address this, we carried out a computational analysis on recently generated time-series RNA-seq datasets from three core-clock knockout (KO) genes (ARNTL, NR1D1, PER2) and WT of a colorectal cancer (CRC) cell line, and time-series RNA-seq datasets for additional CRC and Hodgkin's lymphoma (HL) cells, murine WT, Arntl KO, and Nr1d1/2 KO, and murine SCN WT tissue. The deletion of individual core-clock genes resulted in the loss of circadian expression in crucial spliceosome components such as SF3A1 (in ARNTL(KO)), SNW1 (in NR1D1(KO)), and HNRNPC (in PER2(KO)), which led to a differential pattern of KO-specific AS events. All HCT116(KO) cells showed a rhythmicity loss of a crucial spliceosome gene U2AF1, which was also not rhythmic in higher progression stage CRC and HL cancer cells. AS analysis revealed an increase in alternative first exon events specific to PER2 and NR1D1 KO in HCT116 cells, and a KO-specific change in expression and rhythmicity pattern of AS transcripts related to cancer hallmarks genes including FGFR2 in HCT116_ARNTL(KO), CD44 in HCT116_NR1D1(KO), and MET in HCT116_PER2(KO). KO-specific changes in rhythmic properties of known spliced variants of these genes (e.g. FGFR2 IIIb/FGFR2 IIIc) correlated with epithelial-mesenchymal-transition signalling. Altogether, our bioinformatic analysis highlights a role for the circadian clock in the regulation of AS, and reveals a potential impact of clock disruption in aberrant splicing in cancer hallmark genes.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
cancer cells
en
dc.subject
alternative splicing (AS)
en
dc.subject
core-clock components
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Transcriptome analysis of clock disrupted cancer cells reveals differential alternative splicing of cancer hallmarks genes
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
17
dcterms.bibliographicCitation.doi
10.1038/s41540-022-00225-w
dcterms.bibliographicCitation.journaltitle
npj Systems Biology and Applications
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
8
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
35552415
dcterms.isPartOf.eissn
2056-7189