ArticleNucleic acids research2019
Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- SETD8-mediated mono-methylation of YAP at K76 promotes K48-linked polyubiquitination and degradation to suppress colorectal cancer.Cell death and differentiation · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Histone demethylase JMJD1A protects mice from enteric bacterial infection by upregulating CCL8 expression to recruit macrophages and CD4+ T cells.PLoS pathogens · 2026Article
- Metabolomics and proteomics reveal blocking argininosuccinate synthetase 1 alleviates colitis in mice.Nature communications · 2025Article
- Demystifying the Role of Histone Demethylases in Colorectal Cancer: Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2025Review
- Novel cancer stem cell-targeted retinoid ZSH-512 impedes colorectal cancer progress via KDM3A-mediated epigenetic reprogramming.Innovation (Cambridge (Mass.)) · 2025Article
- Review
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- Epigenetic roles of KDM3B and KDM3C in tumorigenesis and their therapeutic implications.Cell death & disease · 2024Review
- The roles of nuclear orphan receptor NR2F6 in anti-viral innate immunity.PLoS pathogens · 2024Article
- Knockout of KDM3A in MDA-MB-231 breast cancer cells inhibits tumor malignancy and promotes apoptosis.Journal of molecular histology · 2024Article
- YAP represses intestinal inflammation through epigenetic silencing of JMJD3.Clinical epigenetics · 2024Article
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer.Genome biology · 2023Article
- Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC.Clinical epigenetics · 2023Review
- Refined read-out: The hUHRF1 Tandem-Tudor domain prefers binding to histone H3 tails containing K4me1 in the context of H3K9me2/3.Protein science : a publication of the Protein Society · 2023Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Histone Demethylase KDM3 (JMJD1) in Transcriptional Regulation and Cancer Progression.Advances in experimental medicine and biology · 2023Article
- MiR-22-3p regulates the proliferation, migration and invasion of colorectal cancer cells by directly targeting KDM3A through the Hippo pathway.Histology and histopathology · 2022Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hippo pathway is involved in tumorigenesis, and its regulation in cytosol has been extensively studied, but its regulatory mechanisms in the nuclear are not clear. In the current study, using a FBS-inducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. KDM3A promotes gene expression through two mechanisms, one is to upregulate YAP1 expression, and the other is to facilitate H3K27ac on the enhancers of hippo target genes. H3K27ac upregulation is more relevant with gene activation, but not H3K4me3; and KDM3A depletion caused H3K9me2 upregulation mainly on TEAD1-binding enhancers rather than gene bodies, further resulting in H3K27ac decrease, less TEAD1 binding on enhancers and impaired transcription. Moreover, KDM3A is associated with p300 and required for p300 recruitment to enhancers. KDM3A deficiency delayed cancer cell growth and migration, which was rescued by YAP1 expression. KDM3A expression is correlated with YAP1 and hippo target genes in colorectal cancer patient tissues, and may serve as a potential prognosis mark. Taken together, our study reveals novel mechanisms for hippo signaling and enhancer activation, which is critical for tumorigenesis of colorectal cancer.
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