ArticleNucleic acids research2017
RUNX2 expression in thyroid and breast cancer requires the cooperation of three non-redundant enhancers under the control of BRD4 and c-JUN.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Adding pieces to the puzzle of differentiated-to-anaplastic thyroid cancer evolution: the oncogene E2F7.Cell death & disease · 2023Pooled it
- RMzyme: regulations of RNA-modifying enzymes in humans.Signal transduction and targeted therapy · 2026Article
- Exosomes derived from bone marrow mesenchymal stem cells pre-treated with curcumin alleviate osteoporosis by promoting osteogenic differentiation via regulating the METTL3/microRNA-320/RUNX2 signaling pathway.Archives of medical science : AMS · 2026Article
- Epigenetic Regulation of RUNX2 in Bone Mechanobiology.Results and problems in cell differentiation · 2026Review
- RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness.Journal of experimental & clinical cancer research : CR · 2025Article
- Epigenomic Modulators and Thyroid Hormone Receptor β Agonists: A New Paradigm for Tumor Suppression in Thyroid Cancer.Endocrinology · 2025Review
- Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.Biomolecules · 2024Article
- Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.Cell death & disease · 2024Article
- The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions.Oncogene · 2024Review
- BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3.Nature communications · 2024Article
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- METTL16 inhibits papillary thyroid cancer tumorigenicity through mCellular and molecular life sciences : CMLS · 2024Article
- Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.Biomolecules · 2023Review
- Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- Lineage-specific rearrangement of chromatin loops and epigenomic features during adipocytes and osteoblasts commitment.Cell death and differentiation · 2022Article
- Review
- A multimodal integrative approach to model transcriptional addiction of thyroid cancer on RUNX2.Cancer communications (London, England) · 2022Article
- Transcription factor Runx2 changes the expression of some matricellular proteins in metastatic breast cancer cells.Molecular biology reports · 2022Article
- Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.Frontiers in immunology · 2022Review
- Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant reactivation of embryonic pathways is a common feature of cancer. RUNX2 is a transcription factor crucial during embryogenesis that is aberrantly reactivated in many tumors, including thyroid and breast cancer, where it promotes aggressiveness and metastatic spreading. Currently, the mechanisms driving RUNX2 expression in cancer are still largely unknown. Here we showed that RUNX2 transcription in thyroid and breast cancer requires the cooperation of three distantly located enhancers (ENHs) brought together by chromatin three-dimensional looping. We showed that BRD4 controls RUNX2 by binding to the newly identified ENHs and we demonstrated that the anti-proliferative effects of bromodomain inhibitors (BETi) is associated with RUNX2 transcriptional repression. We demonstrated that each RUNX2 ENH is potentially controlled by a distinct set of TFs and we identified c-JUN as the principal pivot of this regulatory platform. We also observed that accumulation of genetic mutations within these elements correlates with metastatic behavior in human thyroid tumors. Finally, we identified RAINs, a novel family of ENH-associated long non-coding RNAs, transcribed from the identified RUNX2 regulatory unit. Our data provide a new model to explain how RUNX2 expression is reactivated in thyroid and breast cancer and how cancer-driving signaling pathways converge on the regulation of this gene.
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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.