ArticleThe Journal of biological chemistry2016
Up-regulation of Histone Methyltransferase, DOT1L, by Matrix Hyaluronan Promotes MicroRNA-10 Expression Leading to Tumor Cell Invasion and Chemoresistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Role of microRNAs in cisplatin response of cancer stem cells.Stem cell research & therapy · 2026Review
- Extracellular Matrix Stiffness Regulates Cancer Stemness in Uveal Melanoma via the PIEZO1-DOT1L Axis.Investigative ophthalmology & visual science · 2025Article
- Molecular insight into histone methylation as a novel target for oral squamous cell carcinoma: future hope in personalised medicine.Journal of Cancer · 2025Review
- Advances in the study of posttranslational modifications of histones in head and neck squamous cell carcinoma.Clinical epigenetics · 2024Review
- Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges.Biomedicines · 2024Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system.Frontiers in immunology · 2024Review
- Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers.Journal of cancer research and clinical oncology · 2023Review
- Fabrication of a Three-Dimensional Spheroid Culture System for Oral Squamous Cell Carcinomas Using a Microfabricated Device.Cancers · 2023Article
- Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor promoting and tumor suppressor roles in ovarian cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Neuronal Dot1l Activity Acts as a Mitochondrial Gene-Repressor Associated with Human Brain Aging via H3K79 Hypermethylation.International journal of molecular sciences · 2023Article
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Mechanisms involved in cancer stem cell resistance in head and neck squamous cell carcinoma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Epigenetic drug library screening reveals targeting DOT1L abrogates NADJournal of pharmaceutical analysis · 2023Article
- Protein acylation: mechanisms, biological functions and therapeutic targets.Signal transduction and targeted therapy · 2022Review
- Non-Coding RNAs in Regulating Plaque Progression and Remodeling of Extracellular Matrix in Atherosclerosis.International journal of molecular sciences · 2022Review
- AberrantJournal of dental sciences · 2022Article
- Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human head and neck squamous cell carcinoma is a solid tumor malignancy associated with major morbidity and mortality. In this study, we determined that human head and neck squamous cell carcinoma-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by a high level of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. Importantly, matrix hyaluronan (HA) induces the up-regulation of stem cell markers that display the hallmark CSC properties. Histone methyltransferase, DOT1L, is also up-regulated by HA in CSCs (isolated from HSC-3 cells). Further analyses indicate that the stimulation of microRNA-10b (miR-10b) expression is DOT1L-specific and HA/CD44-dependent in CSCs. This process subsequently results in the overexpression of RhoGTPases and survival proteins leading to tumor cell invasion and cisplatin resistance. Treatment of CSCs with DOT1L-specific small interfering RNAs (siRNAs) effectively blocks HA/CD44-mediated expression of DOT1L, miR-10b production, and RhoGTPase/survival protein up-regulation as well as reduces tumor cell invasion and enhances chemosensitivity. CSCs were also transfected with a specific anti-miR-10b inhibitor to silence miR-10b expression and block its target functions. Our results demonstrate that the anti-miR-10 inhibitor not only decreases RhoGTPase/survival protein expression and tumor cell invasion, but also increases chemosensitivity in HA-treated CSCs. Taken together, these findings strongly support the contention that histone methyltransferase, DOT1L-associated epigenetic changes induced by HA play pivotal roles in miR-10 production leading to up-regulation of RhoGTPase and survival proteins. All of these events are critically important for the acquisition of cancer stem cell properties, including self-renewal, tumor cell invasion, and chemotherapy resistance in HA/CD44-activated head and neck cancer.
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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.