ArticleCell reports2014
Silencing of the DNA mismatch repair gene MLH1 induced by hypoxic stress in a pathway dependent on the histone demethylase LSD1.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- Trial
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Hesperidin and Hesperetin: Epigenetic-Stemness Crosstalk, Antitumor Mechanisms, Preclinical Data and Translation Barriers.Biomolecules · 2026Review
- Sex differences in gastric cancer mutational burden reflect MLH1-associated epigenetic regulation.BMC cancer · 2026Article
- Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence.Nature communications · 2025Article
- Hypoxia Induces Immunosuppression by Silencing STING in Cancer.Cancer research · 2025Article
- Transposable elements as instructors of the immune system.Nature reviews. Immunology · 2025Review
- Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy.Pathologica · 2025Review
- Increased colorectal cancer risk in prediabetes: A meta-analysis.World journal of diabetes · 2025Article
- Review
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas.Head and neck pathology · 2024Article
- PI3K/AKT Immunoexpression Influences the Prognostic Factors of Patients Diagnosed with Oropharyngeal Squamous Cell Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Deep learning with a small dataset predicts chromatin remodelling contribution to winter dormancy of apple axillary buds.Tree physiology · 2024Article
- Hypoxic adaptation of mitochondria and its impact on tumor cell function.Seminars in cancer biology · 2024Review
- Opposite and Differently Altered Postmortem Changes in H3 and H3K9me3 Patterns in the Rat Frontal Cortex and Hippocampus.Epigenomes · 2024Article
- Cutaneous Metastasis of Transverse Colon Cancer with an Aberrant Pattern of CK7/CK20/CDX2 and High Microsatellite Instability.Internal medicine (Tokyo, Japan) · 2023Article
- Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.Frontiers in cell and developmental biology · 2023Article
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Silencing of MLH1 is frequently seen in sporadic colorectal cancers. We show here that hypoxia causes decreased histone H3 lysine 4 (H3K4) methylation at the MLH1 promoter via the action of the H3K4 demethylases LSD1 and PLU-1 and promotes durable long-term silencing in a pathway that requires LSD1. Knockdown of LSD1 or its corepressor, CoREST, also prevents the resilencing (and associated cytosine DNA methylation) of the endogenous MLH1 promoter in RKO colon cancer cells following transient reactivation by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC). The results demonstrate that hypoxia is a driving force for silencing of MLH1 and that the LSD1/CoREST complex is necessary for this process. The results reveal a mechanism by which hypoxia promotes cancer cell evolution to drive malignant progression through epigenetic modulation. Our findings suggest that LSD1/CoREST acts as a colon cancer oncogene by epigenetically silencing MLH1 and also identify the LSD1/CoREST complex as a potential target for therapy.
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What OpenQuestion holds
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.