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KMID : 0381120230450070901
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Genes and Genomics
2023 Volume.45 No. 7 p.901 ~ p.909
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Transcription of human β-galactoside α2,6-sialyltransferase (hST6Gal I) is downregulated by curcumin through AMPK signaling in human colon carcinoma HCT116 cells
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An So-Young
Kim Kyoung-Sook
Lee Young-Choon
Kim Seok-Ho
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Abstract
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Background : In this study, we observed that in human colon carcinoma HCT116 cells mRNA level of the human β-galactoside α2,6-sialyltransferase (hST6Gal I) was decreased by curcumin. FACS analysis using the α2,6-sialyl-specific lectin (SNA) also showed a noticeable decrease in binding to SNA by curcumin.
Objective : To investigate the mechanism for curcumin-triggered downregulation of hST6Gal I transcription.
Methods : The mRNA levels of nine kinds of hST genes were assessed by RT-PCR after curcumin was treated in HCT116 cells. The level of hST6Gal I product on cell surface was examined by flow cytometry analysis. Luciferase reporter plasmids with 5’-deleted constructs and mutants of the hST6Gal I promoter were transiently transfected into HCT116 cells, and the luciferase activity was measured after treatment with curcumin.
Results : Curcumin led to significant transcriptional repression of the hST6Gal I promoter. Promoter analysis using deletion mutants proved that the ? 303 to ? 189 region of the hST6Gal I promoter is required for transcriptional repression in response to curcumin. Among putative binding sites for transcription factors IK2, GATA1, TCF12, TAL1/E2A, SPT, and SL1 in this region, by site-directed mutagenesis analysis the TAL/E2A binding site (nucleotides ? 266/? 246) was proved to be crucial for curcumin-triggered downregulation of hST6Gal I transcription in HCT116 cells. The transcription activity of hST6Gal I gene in HCT116 cells was markedly suppressed by compound C, an AMP-activated protein kinase (AMPK) inhibitor.
Conclusion : These indicate that gene expression of hST6Gal I in HCT116 cells is controlled through AMPK/TAL/E2A signal pathway.
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KEYWORD
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Curcumin, Human sialyltransferase (hST6Gal I), Human colon carcinoma, TAL1/E2A binding site, Transcriptional repression
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