ArticleExperimental hematology & oncology2020
Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.
Article in Experimental hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma.Blood advances · 2025Article
- Research status of small molecule inhibitors, probes, and degraders of NSDs: a comprehensive review.Future medicinal chemistry · 2025Review
- Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma.Computational and structural biotechnology journal · 2025Article
- GLP and G9a histone methyltransferases as potential therapeutic targets for lymphoid neoplasms.Cancer cell international · 2024Review
- De novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.Epigenetics & chromatin · 2022Article
- Review
- Structure, Activity, and Function of the Protein Lysine Methyltransferase G9a.Life (Basel, Switzerland) · 2021Review
- G9a/GLP targeting in MM promotes autophagy-associated apoptosis and boosts proteasome inhibitor-mediated cell death.Blood advances · 2021Article
- Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis.Cell death discovery · 2021Article
- Insight into the multi-faceted role of the SUV family of H3K9 methyltransferases in carcinogenesis and cancer progression.Biochimica et biophysica acta. Reviews on cancer · 2021Review
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Authors and funding
14 authors.
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Abstract
backgroundMultiple myeloma is an incurable hematological malignancy characterized by a heterogeneous genetic and epigenetic landscape. Although a number of genetic aberrations associated with myeloma pathogenesis, progression and prognosis have been well characterized, the role of many epigenetic aberrations in multiple myeloma remain elusive. G9a, a histone methyltransferase, has been found to promote disease progression, proliferation and metastasis via diverse mechanisms in several cancers. A role for G9a in multiple myeloma, however, has not been previously explored.
methodsExpression levels of G9a/EHMT2 of multiple myeloma cell lines and control cells Peripheral Blood Mononuclear Cells (PBMCs) were analyzed. Correlation of G9a expression and overall survival of multiple myeloma patients were analyzed using patient sample database. To further study the function of G9a in multiple myeloma, G9a depleted multiple myeloma cells were built by lentiviral transduction, of which proliferation, colony formation assays as well as tumorigenesis were measured. RNA-seq of G9a depleted multiple myeloma with controls were performed to explore the downstream mechanism of G9a regulation in multiple myeloma.
resultsG9a is upregulated in a range of multiple myeloma cell lines. G9a expression portends poorer survival outcomes in a cohort of multiple myeloma patients. Depletion of G9a inhibited proliferation and tumorigenesis in multiple myeloma. RelB was significantly downregulated by G9a depletion or small molecule inhibition of G9a/GLP inhibitor UNC0642, inducing transcription of proapoptotic genes
conclusionsIn this study, we demonstrated that G9a is upregulated in most multiple myeloma cell lines. Furthermore, G9a loss-of-function analysis provided evidence that G9a contributes to multiple myeloma cell survival and proliferation. This study found that G9a interacts with NF-κB pathway as a key regulator of RelB in multiple myeloma and regulates RelB-dependent multiple myeloma survival. G9a therefore is a promising therapeutic target for multiple myeloma.
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