ArticleThe Journal of clinical investigation2018
Cyclin D1 overexpression induces global transcriptional downregulation in lymphoid neoplasms.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Review
- TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.Cancer biology & therapy · 2024Article
- Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches.International journal of molecular sciences · 2024Article
- A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription.Oncogenesis · 2024Article
- Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against hypertranscription.Nature communications · 2023Article
- Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations.Blood cancer journal · 2023Article
- Therapeutic Potential of Nanomedicine in Management of Alzheimer's Disease and Glioma.International journal of nanomedicine · 2023Review
- Review
- Insights into the mechanisms underlying aberrant SOX11 oncogene expression in mantle cell lymphoma.Leukemia · 2022Article
- Disruption of pathways regulated by Integrator complex in Galloway-Mowat syndrome due to WDR73 mutations.Scientific reports · 2021Article
- Loss of Mediator complex subunit 13 (MED13) promotes resistance to alkylation through cyclin D1 upregulation.Nucleic acids research · 2021Article
- Gene Methylation and Silencing of WIF1 Is a Frequent Genetic Abnormality in Mantle Cell Lymphoma.International journal of molecular sciences · 2021Article
- A Cyclin D1-Dependent Transcriptional Program Predicts Clinical Outcome in Mantle Cell Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Review
- Molecular Pathogenesis of Mantle Cell Lymphoma.Hematology/oncology clinics of North America · 2020Review
- The double dealing of cyclin D1.Cell cycle (Georgetown, Tex.) · 2020Review
- Cyclin F Downregulation Affects Epithelial-Mesenchymal Transition Increasing Proliferation and Migration of the A-375 Melanoma Cell Line.Cancer management and research · 2020Article
- Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology.Expert review of anticancer therapy · 2019Review
- Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin D1 is an oncogene frequently overexpressed in human cancers that has a dual function as cell cycle and transcriptional regulator, although the latter is widely unexplored. Here, we investigated the transcriptional role of cyclin D1 in lymphoid tumor cells with cyclin D1 oncogenic overexpression. Cyclin D1 showed widespread binding to the promoters of most actively transcribed genes, and the promoter occupancy positively correlated with the transcriptional output of targeted genes. Despite this association, the overexpression of cyclin D1 in lymphoid cells led to a global transcriptional downmodulation that was proportional to cyclin D1 levels. This cyclin D1-dependent global transcriptional downregulation was associated with a reduced nascent transcription and an accumulation of promoter-proximal paused RNA polymerase II (Pol II) that colocalized with cyclin D1. Concordantly, cyclin D1 overexpression promoted an increase in the Poll II pausing index. This transcriptional impairment seems to be mediated by the interaction of cyclin D1 with the transcription machinery. In addition, cyclin D1 overexpression sensitized cells to transcription inhibitors, revealing a synthetic lethality interaction that was also observed in primary mantle cell lymphoma cases. This finding of global transcriptional dysregulation expands the known functions of oncogenic cyclin D1 and suggests the therapeutic potential of targeting the transcriptional machinery in cyclin D1-overexpressing tumors.
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Registered trials
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.