ArticleBlood2016
Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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.
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Who cites it
75 citing papers in PubMed, 123 citations in OpenAlex.
- Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women.International journal of molecular sciences · 2019Trial
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Article
- Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.Translational oncology · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Chlorogenic acid targets SIRT6 to relieve UVB - induced UV damage.Archives of dermatological research · 2025Article
- The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.Cancers · 2025Review
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- The ABA/LANCL1-2 Hormone/Receptors System Controls ROS Production in Cardiomyocytes through ERRα.Biomedicines · 2024Article
- 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
- SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs.Cardiovascular toxicology · 2024Review
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
- The Role of Sirtuin 6 in the Deacetylation of Histone Proteins as a Factor in the Progression of Neoplastic Disease.International journal of molecular sciences · 2023Review
- SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.Scientific reports · 2023Article
- Targeting the deacetylase SIRT6 unveils spliceosome deregulation as exploitable vulnerability for aggressive myeloma.Blood advances · 2023Article
- CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NADAntioxidants (Basel, Switzerland) · 2023Article
- SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy.International journal of medical sciences · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Multiple myeloma (MM) is characterized by a highly unstable genome, with aneuploidy observed in nearly all patients. The mechanism causing this karyotypic instability is largely unknown, but recent observations have correlated these abnormalities with dysfunctional DNA damage response. Here, we show that the NAD(+)-dependent deacetylase SIRT6 is highly expressed in MM cells, as an adaptive response to genomic stability, and that high SIRT6 levels are associated with adverse prognosis. Mechanistically, SIRT6 interacts with the transcription factor ELK1 and with the ERK signaling-related gene. By binding to their promoters and deacetylating H3K9 at these sites, SIRT6 downregulates the expression of mitogen-activated protein kinase (MAPK) pathway genes, MAPK signaling, and proliferation. In addition, inactivation of ERK2/p90RSK signaling triggered by high SIRT6 levels increases DNA repair via Chk1 and confers resistance to DNA damage. Using genetic and biochemical studies in vitro and in human MM xenograft models, we show that SIRT6 depletion both enhances proliferation and confers sensitization to DNA-damaging agents. Our findings therefore provide insights into the functional interplay between SIRT6 and DNA repair mechanisms, with implications for both tumorigenesis and the treatment of MM.
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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.