ArticleThe Journal of clinical investigation2016
Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis.Science advances · 2022Pooled it
- Virtual Screening-Guided Identification of Candidate USP7-Inhibitory Scaffolds Exhibiting Antiproliferative Activity.Pharmaceuticals (Basel, Switzerland) · 2026Article
- BRCC3 promotes progression and immune evasion in non-small cell lung cancer through regulation of PD-L1 and B7-H3.Journal of molecular histology · 2026Article
- Ubiquitin-mediated stabilization of KDM5B drives chemoresistance via repression of dual-specificity phosphatase 4 in ovarian cancer.Signal transduction and targeted therapy · 2026Article
- USP7 facilitates brain tumor survival upon glucose deprivation by regulating phosphofructokinase muscle-type nuclear translocation in mice.PLoS biology · 2026Article
- KDM7B-mediated demethylation of RNF113A regulates small cell lung cancer sensitivity to alkylation damage.bioRxiv : the preprint server for biology · 2026Article
- CCND1 Stability Regulated by USP7 Deubiquitination Controls Glioma Radioresistance via Ferroptosis.Analytical cellular pathology (Amsterdam) · 2026Article
- USP7 sustains hematopoietic stem cell homeostasis partially via PU.1 stabilization.International journal of biological sciences · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- HER3 promotes triple-negative breast cancer progression by upregulating PHF8 via miR-34b-5p-dependent mechanism.Cell death & disease · 2025Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Therapeutic inhibition of USP7 promotes antitumor immune responses.Journal for immunotherapy of cancer · 2025Article
- Article
- Review
- Genome-wide CRISPR screening identifies PHF8 as an effective therapeutic target for KRAS- or BRAF-mutant colorectal cancers.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- PHF8 facilitates transcription recovery following DNA double-strand break repair.Nucleic acids research · 2024Article
- PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers.Epigenomes · 2024Review
- MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer.Cell death & disease · 2024Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The histone demethylase PHF8 has been implicated in multiple pathological disorders, including X-linked mental retardation and tumorigenesis. However, it is not clear how the abundance and function of PHF8 are regulated. Here, we report that PHF8 physically associates with the deubiquitinase USP7. Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation. The USP7-encoding gene was also transcriptionally regulated by PHF8, via positive feedback. USP7 was overexpressed in breast carcinomas, and the level of expression positively correlated with expression of PHF8 and cyclin A2 and with the histological grade of breast cancer. We showed that USP7 promotes breast carcinogenesis by stabilizing PHF8 and upregulating cyclin A2 and that the interaction between USP7 and PHF8 is augmented during DNA damage. Moreover, USP7-promoted PHF8 stabilization conferred cellular resistance to genotoxic insults and was required for the recruitment of BLM and KU70, which are both essential for DNA double-strand break repair. Our study mechanistically links USP7 to epigenetic regulation and DNA repair. Moreover, these data support the pursuit of USP7 and PHF8 as potential targets for breast cancer intervention, especially in combination with chemo- or radiotherapies.
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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.