ArticleCancer research2013
Menin epigenetically represses Hedgehog signaling in MEN1 tumor syndrome.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The trial behind it
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Who cites it
61 citing papers in PubMed, 101 citations in OpenAlex.
- Inhibition of SIRT7 Overcomes Radioresistance in Pancreatic Neuroendocrine Tumors by Reactivating MEN1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- Targeting menin in lysine methyltransferase 2A/nucleophosmin-mutated leukemia: A novel strategy from epigenetic dysregulation to clinical therapy (Review).Oncology letters · 2025Review
- Endometrial stromal Menin supports endometrial receptivity by maintaining homeostasis of WNT signaling pathway through H3K4me3 during WOI.Communications biology · 2025Article
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- Menin maintains lysosomal and mitochondrial homeostasis through epigenetic mechanisms in lung cancer.Cell death & disease · 2025Article
- Menin in Cancer.Genes · 2024Review
- MEN1 Deficiency-Driven Activation of the β-Catenin-MGMT Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers Temozolomide Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Menin Reduces Parvalbumin Expression and is Required for the Anti-Depressant Function of Ketamine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.The Journal of clinical endocrinology and metabolism · 2023Article
- Research progress on PRMTs involved in epigenetic modification and tumour signalling pathway regulation (Review).International journal of oncology · 2023Review
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors.Acta biochimica et biophysica Sinica · 2022Article
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- Genetic Deletion of Menin in Mouse Mesenchymal Stem Cells: An Experimental and Computational Analysis.JBMR plus · 2022Article
- Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.International journal of molecular sciences · 2022Review
- Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation.Frontiers in oncology · 2022Review
- Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors.Frontiers in oncology · 2022Review
- Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumor syndrome that includes susceptibility to pancreatic islet tumors. This syndrome results from mutations in the MEN1 gene, encoding menin. Although menin acts as an oncogenic cofactor for mixed lineage leukemia (MLL) fusion protein-mediated histone H3 lysine 4 methylation, the precise basis for how menin suppresses gene expression and proliferation of pancreatic beta cells remains poorly understood. Here, we show that menin ablation enhances Hedgehog signaling, a proproliferative and oncogenic pathway, in murine pancreatic islets. Menin directly interacts with protein arginine methyltransferase 5 (PRMT5), a negative regulator of gene transcription. Menin recruits PRMT5 to the promoter of the Gas1 gene, a crucial factor for binding of Sonic Hedgehog (Shh) ligand to its receptor PTCH1 and subsequent activation of the Hedgehog signaling pathway, increases repressive histone arginine symmetric dimethylation (H4R3m2s), and suppresses Gas1 expression. Notably, MEN1 disease-related menin mutants have reduced binding to PRMT5, and fail to impart the repressive H4R3m2s mark at the Gas1 promoter, resulting in its elevated expression. Pharmacologic inhibition of Hedgehog signaling significantly reduces proliferation of insulinoma cells, and expression of Hedgehog signaling targets including Ptch1, in MEN1 tumors of mice. These findings uncover a novel link between menin and Hedgehog signaling whereby menin/PRMT5 epigenetically suppresses Hedgehog signaling, revealing it as a target for treating MEN1 tumors.
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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.