ArticleOncotarget2016
Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Pooled it
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- Domain-derived knowledge enabled machine learning and functional characterization of cancer-associated RNA methylation sites.BMC bioinformatics · 2026Article
- The Regulatory Role of mCells · 2026Review
- m6A RNA methylation regulator-associated genes drive metastasis and immune cell infiltration in skin cutaneous melanoma.Oncology letters · 2025Article
- FTO promotes the progression of triple-negative breast cancer by regulating the m6A methylation of NFKBIE.Clinical and experimental medicine · 2025Article
- Comprehensive profiling of RNA modification-related genes identifies RNA mExperimental & molecular medicine · 2025Article
- Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.Journal of experimental & clinical cancer research : CR · 2025Review
- Aberrant overexpression of m6A writer and reader genes in pediatric B-Cell Acute Lymphoblastic Leukemia (B-ALL).Translational oncology · 2025Article
- Hsa_circ_0101308 adjusted by N6-methyladenosine (mCancer biomarkers : section A of Disease markers · 2025Article
- m6A-lncRNA landscape highlights reduced levels of m6A modification in glioblastoma as compared to low-grade glioma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways.Molecular medicine (Cambridge, Mass.) · 2025Review
- ALKBH5 Promotes Breast Cancer Stemness Through Regulating Wnt/β-Catenin Signaling.Breast cancer (Dove Medical Press) · 2025Article
- CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia.Theranostics · 2025Article
- Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation.Cell reports · 2024Article
- Interpretable deep cross networks unveiled common signatures of dysregulated epitranscriptomes across 12 cancer types.Molecular therapy. Nucleic acids · 2024Article
- The Role of N6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility.Genomics, proteomics & bioinformatics · 2024Review
- Functions and mechanisms of RNA mInternational journal of oncology · 2024Review
- The role of the ALKBH5 RNA demethylase in invasive breast cancer.Discover oncology · 2024Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification. Although hypoxia induced the BCSC phenotype in all breast-cancer cell lines analyzed, it did so through variable induction of pluripotency factors and ALKBH5 or ZNF217. However, in every breast cancer line, the hypoxic induction of pluripotency factor and ALKBH5 or ZNF217 expression was HIF-dependent. Immunohistochemistry revealed that expression of HIF-1α and ALKBH5 was concordant in all human breast cancer biopsies analyzed. ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. Thus, HIFs stimulate pluripotency factor expression and BCSC specification by negative regulation of RNA methylation.
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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.