ArticleCell research2022
Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia.
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Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
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29 citing papers in PubMed, 39 citations in OpenAlex.
- Exacerbation of renal interstitial fibrosis by the UHRF1/G9a axis through epigenetic silencing of KLF15.Renal failure · 2026Article
- Oncogenic DHX15 mutation enhances mitochondrial metabolism and sustains leukemia stemness.Leukemia · 2026Article
- Article
- Selective cellular localization of UHRF1 safeguards mammalian zygotic genome activation and early embryonic development.Cell discovery · 2026Article
- MXD4 enhances resistance to KRAS G12C-targeted therapy in lung adenocarcinoma by suppressing ACSL4-mediated ferroptosis.Respiratory research · 2026Article
- UHRF1 as an epigenetic therapeutic target in Cancer.Molecular biology reports · 2026Review
- A Hybrid compound H93 treats prostate cancer by directly binding UHRF1 and promoting protein dimerization.Communications chemistry · 2025Article
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML.bioRxiv : the preprint server for biology · 2025Article
- Discovery and Characterization of Uracil Derivatives Targeting the Set-and-Ring Domain of UHRF1.Journal of chemical information and modeling · 2025Article
- Single-cell sequencing reveals the expansion and diversity of T cell subsets in the bone marrow microenvironment of chronic myeloid leukemia.Genes & diseases · 2025Article
- The novel ferroptosis-inducing molecule can inhibit the progression of BC by regulating the ubiquitination of UHRF1.Epigenomics · 2025Article
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1.International journal of molecular sciences · 2025Article
- Exploring the Anti-Leukemic Effect of the Synthetic Retinoid ST1926 on Malignant T Cells: A Comprehensive Proteomics Approach.International journal of molecular sciences · 2025Article
- SAP30, a novel autophagy regulatory gene in neuroblastoma.Molecular therapy. Oncology · 2025Article
- Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs.NAR genomics and bioinformatics · 2025Article
- SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer.Cell & bioscience · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.Scientific reports · 2024Article
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Authors and funding
42 authors at 7 institutions in 2 countries.
Cheng-Long Hu *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-2928-2625
Bing-Yi Chen *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Zijuan Li *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Tianbiao Yang *Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chun-Hui Xu *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-3836-3179
Ruirui YangDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Peng-Cheng YuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jingyao ZhaoState Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Ting LiuKey Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Na LiuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Bin ShanSchool of Pharmacy, Fudan University, Shanghai, China.
Qunling ZhangDepartment of lymphoma, Fudan University Shanghai Cancer Center, Shanghai, China.
Junhong SongKey Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ming-Yue FeiCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-7699-7842
Li-Juan ZongCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jia-Ying ZhangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ji-Chuan WuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Shu-Bei ChenShanghai Jiao Tong University School of Life Sciences and Biotechnology, Shanghai, China.
Yong WangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Binhe ChangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Dan HouCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ping LiuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yilun JiangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xiya LiCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xinchi ChenCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Chu-Han DengCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yi-Yi RenCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Roujia WangDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Jiacheng JinDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Kai XueState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ying ZhangHospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Meirong DuHospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Jun ShiDepartment of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ling-Yun WuDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Chun-Kang ChangDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Shuhong ShenKey Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Zhu ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sai-Juan ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaolong LiuState Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. liux@sibcb.ac.cn.ORCID 0000-0001-7358-0366
Xiao-Jian SunState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xjsun@sibs.ac.cn.ORCID 0000-0001-8826-4614
Mingyue ZhengDrug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. myzheng@simm.ac.cn.ORCID 0000-0002-3323-3092
Lan WangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. lwang@sibs.ac.cn.ORCID 0000-0003-3545-5059
Shanghai Institute of Nutrition and Health · CNShanghai Jiao Tong University · CNFudan University · CNCenter for Excellence in Molecular Cell Science · CNChinese Academy of Sciences · CNShanghai Institute of Materia Medica · CNShanghai Medical College of Fudan University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A-associated protein 30 (SAP30) through two critical amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Further knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, our study reveals the mechanisms for altered epigenetic programs in AML and provides a promising targeted therapeutic strategy against AML.
Indexed as
Leukemia, Myeloid, AcuteBasic Helix-Loop-Helix ProteinsCarcinogenesisCCAAT-Enhancer-Binding ProteinsHistone DeacetylasesHumansRepressor ProteinsUbiquitin-Protein LigasesBasic Helix-Loop-Helix ProteinsCCAAT-Enhancer-Binding ProteinsHistone DeacetylasesMXD4 protein, humanRepressor ProteinsSAP30 protein, humanUbiquitin-Protein LigasesUHRF1 protein, human
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