ArticleProceedings of the National Academy of Sciences of the United States of America2008
Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 95 citations in OpenAlex.
- A de novo assembly based fusion gene detection concept based on DNA-seq data of 100 Ewing sarcoma cases.Briefings in bioinformatics · 2026Article
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- Impact of G1 phase kinetics on the acquisition of stemness in cancer cells: the critical role of cyclin D.Molecular biology reports · 2025Review
- ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3.Molecular cancer research : MCR · 2024Article
- Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.Biomarker research · 2024Review
- ETS1, a target gene of the EWSR1::FLI1 fusion oncoprotein, regulates the expression of the focal adhesion protein TENSIN3.bioRxiv : the preprint server for biology · 2023Article
- Aberrant Cyclin D1 splicing in cancer: from molecular mechanism to therapeutic modulation.Cell death & disease · 2023Review
- Influence of cyclin D1 splicing variants expression on breast cancer chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.Journal of cellular and molecular medicine · 2023Article
- Splice variants denote differences between a cancer stem cell side population of EWSR1‑ERG‑based Ewing sarcoma cells, its main population and EWSR1‑FLI‑based cells.International journal of molecular medicine · 2022Article
- Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcomaFrontiers in genetics · 2022Article
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Alternative polyadenylation: An untapped source for prostate cancer biomarkers and therapeutic targets?Asian journal of urology · 2021Review
- Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer.Medical oncology (Northwood, London, England) · 2021Review
- ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.Nucleic acids research · 2021Article
- High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma.Cancers · 2020Article
- Development of an Ewing sarcoma cell line with resistance to EWS‑FLI1 inhibitor YK‑4‑279.Molecular medicine reports · 2020Article
- Article
- Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies.Cancer metastasis reviews · 2019Review
- Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma.Annals of translational medicine · 2019Article
- CCND1 Splice Variant as A Novel Diagnostic and Predictive Biomarker for Thyroid Cancer.Cancers · 2018Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pre-mRNA splicing and polyadenylation are tightly connected to transcription, and transcriptional stimuli and elongation dynamics can affect mRNA maturation. However, whether this regulatory mechanism has a physio/pathological impact is not known. In cancer, where splice variant expression is often deregulated, many mutated oncogenes are transcriptional regulators. In particular, the Ewing sarcoma (EwSa) oncogene, resulting from a fusion of the EWS and FLI1 genes, encodes a well characterized transcription factor. EWS-FLI1 directly stimulates transcription of the CCND1 protooncogene encoding cyclin D1a and a less abundant but more oncogenic splice isoform, D1b. We show that, although both EWS and EWS-FLI1 enhance cyclin D1 gene expression, they regulate the D1b/D1a transcript ratio in an opposite manner. Detailed analyses of RNA polymerase dynamics along the gene and of the effects of an inhibitor of elongation show that EWS-FLI1 favors D1b isoform expression by decreasing the elongation rate, whereas EWS has opposite effects. As a result, the D1b/D1a ratio is elevated in EwSa cell lines and tumors. The endogenous D1b protein is enriched in nuclei, where the oncogenic activity of cyclin D1 is known to occur, and depleting D1b in addition to D1a results in a stronger reduction of EwSa cell growth than depleting D1a only. These data show that elevated expression of a splice isoform in cancer can be due to an alteration of the transcription process by a mutated transcriptional regulator and provide evidence for a physio/pathological impact of the coupling between transcription and mRNA maturation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.