ArticleOncogene2016
MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 91 citations in OpenAlex.
- NSD2 upregulation is driven by high-risk HPV E6/E7 and disrupts epithelial differentiation in HPV-associated head and neck cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Article
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Discovery of NSD2 non-histone substrates and design of a super-substrate.Communications biology · 2024Article
- Mechanisms of the role of proto-oncogene activation in promoting malignant transformation of mature B cells.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Particulate matter composition drives differential molecular and morphological responses in lung epithelial cells.PNAS nexus · 2024Article
- Association of WHSC1/NSD2 and T-cell infiltration with prostate cancer metastasis and prognosis.Scientific reports · 2023Article
- Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer.Cancers · 2023Article
- Identifying Suitable Reference Gene Candidates for Quantification of DNA Damage-Induced Cellular Responses in Human U2OS Cell Culture System.Biomolecules · 2023Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- NSD3, a member of nuclear receptor-binding SET domain family, is a potential prognostic biomarker for pancreatic cancer.Cancer medicine · 2023Article
- A Dual Role for FADD in Human Precursor T-Cell Neoplasms.International journal of molecular sciences · 2022Article
- Understanding the Roles of the NSD Protein Methyltransferases in Head and Neck Squamous Cell Carcinoma.Genes · 2022Review
- Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.Translational oncology · 2022Article
- The Role of DNA Repair in Genomic Instability of Multiple Myeloma.International journal of molecular sciences · 2022Review
- Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loopActa pharmaceutica Sinica. B · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, believed to be the driving factor in the pathogenesis of this MM subtype. MMSET overexpression in MM leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3), as well as changes in proliferation, gene expression and chromatin accessibility. Prior work linked methylation of histones to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET may play a role in DNA damage repair and response. In U2OS cells, we found that MMSET is required for efficient non-homologous end joining as well as homologous recombination. Loss of MMSET led to loss of expression of several DNA repair proteins, as well as decreased recruitment of DNA repair proteins to sites of DNA double-strand breaks (DSBs). By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline. Upon addition of a DNA-damaging agent, MMSET-high cells repaired DNA damage at an enhanced rate and continued to proliferate, whereas MMSET-low cells accumulated DNA damage and entered cell cycle arrest. In a murine xenograft model using t(4;14)+ KMS11 MM cells harboring an inducible MMSET shRNA, depletion of MMSET enhanced the efficacy of chemotherapy, inhibiting tumor growth and extending survival. These findings help explain the poorer prognosis of t(4;14) MM and further validate MMSET as a potential therapeutic target in MM and other cancers.
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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.