ArticleThe Journal of biological chemistry2019
Elevated histone H3 acetylation and loss of the Sp1-HDAC1 complex de-repress the GM2-synthase gene in renal cell carcinoma.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Unveiling the epigenetic landscape: transforming renal cell carcinoma treatment.Clinical epigenetics · 2026Review
- Ganglioside therapy in cancer molecular insights and therapeutic opportunities.Discover oncology · 2025Review
- LncRNA EGFR‑AS1 promotes lung cancer cell proliferation, invasion and metastasis via regulation of miR‑449a/HDAC1.Experimental and therapeutic medicine · 2025Article
- HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Glycosylation in Cancer.Handbook of experimental pharmacology · 2025Review
- Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer.Cancer cell international · 2024Article
- CD38 in SLE CD4 T cells promotes CaNature communications · 2024Article
- Wide-Targeted Semi-Quantitative Analysis of Acidic Glycosphingolipids in Cell Lines and Urine to Develop Potential Screening Biomarkers for Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
- Synergistic antitumor efficacy of gemcitabine and cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via Sp1-SAT1-polyamine metabolism pathway.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Sas3-mediated histone acetylation regulates effector gene activation in a fungal plant pathogen.mBio · 2023Article
- Endothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice.Nature communications · 2023Article
- P300/SP1 complex mediating elevated METTL1 regulates CDK14 mRNA stability via internal m7G modification in CRPC.Journal of experimental & clinical cancer research : CR · 2023Article
- A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids.International journal of molecular sciences · 2023Article
- Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice.Nature communications · 2023Article
- Multi-dimensional role of gangliosides in modulating cancer hallmarks and their prospects in targeted cancer therapy.Frontiers in pharmacology · 2023Review
- Insight into mechanisms of pig lncRNA FUT3-AS1 regulating E. coli F18-bacterial diarrhea.PLoS pathogens · 2022Article
- Review
- Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription.International journal of molecular sciences · 2021Review
- Epigenetic Regulation of Glycosylation in Cancer and Other Diseases.International journal of molecular sciences · 2021Review
- Elucidation of the Hdac2/Sp1/Molecular therapy. Nucleic acids · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GM2-synthase produces sialic acid-containing glycosphingolipids called gangliosides, and its mRNA overexpression and the gangliosides it generates are linked to tumor progression, migration, and suppression of tumor-specific host immune responses. However, the mechanism underlying GM2-synthase de-repression in renal cell carcinoma (RCC) is poorly understood. Here, we demonstrate that higher GM2-synthase mRNA expression levels in various cancer cells and in human RCC tumors correlate with higher histone acetylation levels (H3K9, H3K14, or both) at region +38/+187 relative to the transcription start site (TSS) of the GM2-synthase gene than in normal kidney epithelial (NKE) cells or healthy adjacent tissues. An increase in GM2-synthase mRNA expression in cells treated with a histone deacetylase (HDAC) inhibitor was accompanied by increased histone acetylation levels at this promoter region. DNA methylation around the TSS was absent in both RCC cell lines and NKE cells. Of note, both the transcription factor Sp1 and corepressor HDAC1 associated with the +38/+187 region when the GM2-synthase gene was repressed in NKE and tumor-adjacent tissues, indicating plausible site-specific repressive roles of HDAC1 and Sp1 in GM2-synthase mRNA expression. Site-directed mutagenesis of the Sp1-binding site within the +38/+187 region relieved repressed luciferase activity of this region by limiting HDAC1 recruitment. Moreover, Sp1 or HDAC1 knock down increased GM2-synthase transcription, and butyrate-mediated activation of GM2-synthase mRNA expression in SK-RC-45 cells was accompanied by Sp1 and HDAC1 loss from the +38/+187 region. Taken together, we have identified an epigenetic mechanism for the de-repression of the GM2-synthase gene in RCC.
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