The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER
Open accessAbstract
MicroRNAs are small regulatory RNAs that post transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet, the underlying mechanisms are not well understood. Here we identify tumour hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumour stem cell phenotypes that may underlie poor outcome in breast cancer. Reduced expression of DICER—responsible for the processing of microRNA precursors—was previously linked to poor clinical outcomes in cancer patients. Here, the authors uncover an epigenetic mechanism by which hypoxia suppresses DICER expression and deregulates the miR-200-Zeb1 circuit in breast cancer to promote the tumour phenotype.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
METABRIC Group, Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., et al. (2012) · Nature · doi:10.1038/nature10983 · Cited by 6,097
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Bernstein, B. E., Meissner, A., & Lander, E. S. (2007) · Cell · doi:10.1016/j.cell.2007.01.033 · Cited by 2,086
Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells
Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., Shi, Q., Cao, Y., Lathia, J., McLendon, R. E., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.018 · Cited by 1,354
Direct regulation of TWIST by HIF-1α promotes metastasis
Yang, M.-H., Wu, M.-Z., Chiou, S.-H., Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., & Wu, K.-J. (2008) · Nature Cell Biology · doi:10.1038/ncb1691 · Cited by 1,345
EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., & Helin, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg542 · Cited by 1,196
Hypoxia-Inducible Factors, Stem Cells, and Cancer
Keith, B., & Simon, M. C. (2007) · Cell · doi:10.1016/j.cell.2007.04.019 · Cited by 1,179
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173
Cited by
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
Rupaimoole, R., & Slack, F. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.246 · Cited by 4,741
MicroRNA biogenesis pathways in cancer
Lin, S., & Gregory, R. I. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3932 · Cited by 2,112
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869
Advances in Hypoxia-Inducible Factor Biology
Choudhry, H., & Harris, A. L. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.005 · Cited by 868
Self-citationIntra-tumor heterogeneity from a cancer stem cell perspective
Prasetyanti, P. R., & Medema, J. P. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0600-4 · Cited by 800
Metadata
- Authors
- van den Beucken, T., Koch, E., Chu, K., Rupaimoole, R., Prickaerts, P., Adriaens, M., Voncken, J. W., Harris, A. L., Buffa, F. M., Haider, S., Starmans, M. H. W., Yao, C. Q., Ivan, M., Ivan, C., Pecot, C. V., Boutros, P. C., Sood, A. K., Koritzinsky, M., & Wouters, B. G.
- Venue
- Nature Communications
- Published
- 2014-10-29
- Volume
- 5
- Issue
- 1
- Pages
- 5203-5203
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2078160295
- Cited by
- 229
- References
- 16
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. https://app.cochat.ai/papers/10.1038/ncomms6203
- The paper
- van den Beucken, T., Koch, E., Chu, K., Rupaimoole, R., Prickaerts, P., Adriaens, M., Voncken, J. W., Harris, A. L., Buffa, F. M., Haider, S., Starmans, M. H. W., Yao, C. Q., Ivan, M., Ivan, C., Pecot, C. V., Boutros, P. C., Sood, A. K., Koritzinsky, M., & Wouters, B. G. (2014). Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nature Communications. https://doi.org/10.1038/ncomms6203
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
