FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2901674023> ?p ?o ?g. }

• W2901674023 endingPage "1018" @default.
• W2901674023 startingPage "1005" @default.
• W2901674023 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. 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." @default.
• W2901674023 created "2018-11-29" @default.
• W2901674023 creator A5013278228 @default.
• W2901674023 creator A5015756618 @default.
• W2901674023 creator A5030420000 @default.
• W2901674023 creator A5037188554 @default.
• W2901674023 creator A5041854743 @default.
• W2901674023 date "2019-01-01" @default.
• W2901674023 modified "2023-10-15" @default.
• W2901674023 title "Elevated histone H3 acetylation and loss of the Sp1–HDAC1 complex de-repress the GM2-synthase gene in renal cell carcinoma" @default.
• W2901674023 cites W128066484 @default.
• W2901674023 cites W1585646325 @default.
• W2901674023 cites W1966692313 @default.
• W2901674023 cites W1972953239 @default.
• W2901674023 cites W1981256215 @default.
• W2901674023 cites W1991040915 @default.
• W2901674023 cites W1992397774 @default.
• W2901674023 cites W2002031850 @default.
• W2901674023 cites W2004408281 @default.
• W2901674023 cites W2013573837 @default.
• W2901674023 cites W2016403221 @default.
• W2901674023 cites W2016450815 @default.
• W2901674023 cites W2023997559 @default.
• W2901674023 cites W2053110665 @default.
• W2901674023 cites W2063110349 @default.
• W2901674023 cites W2071981322 @default.
• W2901674023 cites W2074174832 @default.
• W2901674023 cites W2083245183 @default.
• W2901674023 cites W2083704810 @default.
• W2901674023 cites W2092733067 @default.
• W2901674023 cites W2094528164 @default.
• W2901674023 cites W2095884976 @default.
• W2901674023 cites W2097342284 @default.
• W2901674023 cites W2097633205 @default.
• W2901674023 cites W2099356747 @default.
• W2901674023 cites W2107709399 @default.
• W2901674023 cites W2113210499 @default.
• W2901674023 cites W2122745942 @default.
• W2901674023 cites W2127265808 @default.
• W2901674023 cites W2130033695 @default.
• W2901674023 cites W2130042720 @default.
• W2901674023 cites W2139122477 @default.
• W2901674023 cites W2147524392 @default.
• W2901674023 cites W2150162153 @default.
• W2901674023 cites W2159479890 @default.
• W2901674023 cites W2163219838 @default.
• W2901674023 cites W2167098315 @default.
• W2901674023 cites W2170471875 @default.
• W2901674023 cites W2198199336 @default.
• W2901674023 cites W2263210824 @default.
• W2901674023 cites W2272594669 @default.
• W2901674023 cites W2315794124 @default.
• W2901674023 doi "https://doi.org/10.1074/jbc.ra118.004485" @default.
• W2901674023 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6341395" @default.
• W2901674023 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30463940" @default.
• W2901674023 hasPublicationYear "2019" @default.
• W2901674023 type Work @default.
• W2901674023 sameAs 2901674023 @default.
• W2901674023 citedByCount "24" @default.
• W2901674023 countsByYear W29016740232019 @default.
• W2901674023 countsByYear W29016740232020 @default.
• W2901674023 countsByYear W29016740232021 @default.
• W2901674023 countsByYear W29016740232022 @default.
• W2901674023 countsByYear W29016740232023 @default.
• W2901674023 crossrefType "journal-article" @default.
• W2901674023 hasAuthorship W2901674023A5013278228 @default.
• W2901674023 hasAuthorship W2901674023A5015756618 @default.
• W2901674023 hasAuthorship W2901674023A5030420000 @default.
• W2901674023 hasAuthorship W2901674023A5037188554 @default.
• W2901674023 hasAuthorship W2901674023A5041854743 @default.
• W2901674023 hasBestOaLocation W29016740231 @default.
• W2901674023 hasConcept C104317684 @default.
• W2901674023 hasConcept C119157956 @default.
• W2901674023 hasConcept C153911025 @default.
• W2901674023 hasConcept C185592680 @default.
• W2901674023 hasConcept C2778305200 @default.
• W2901674023 hasConcept C502942594 @default.
• W2901674023 hasConcept C55493867 @default.
• W2901674023 hasConcept C64927066 @default.
• W2901674023 hasConcept C71723506 @default.
• W2901674023 hasConcept C85240754 @default.
• W2901674023 hasConcept C86803240 @default.
• W2901674023 hasConceptScore W2901674023C104317684 @default.
• W2901674023 hasConceptScore W2901674023C119157956 @default.
• W2901674023 hasConceptScore W2901674023C153911025 @default.
• W2901674023 hasConceptScore W2901674023C185592680 @default.
• W2901674023 hasConceptScore W2901674023C2778305200 @default.
• W2901674023 hasConceptScore W2901674023C502942594 @default.
• W2901674023 hasConceptScore W2901674023C55493867 @default.
• W2901674023 hasConceptScore W2901674023C64927066 @default.
• W2901674023 hasConceptScore W2901674023C71723506 @default.
• W2901674023 hasConceptScore W2901674023C85240754 @default.
• W2901674023 hasConceptScore W2901674023C86803240 @default.
• W2901674023 hasFunder F4320320717 @default.
• W2901674023 hasIssue "3" @default.
• W2901674023 hasLocation W29016740231 @default.
• W2901674023 hasLocation W29016740232 @default.
• W2901674023 hasLocation W29016740233 @default.

• next