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Journal: The Journal of Biological Chemistry
Article Title: KRAS G12D mutation promotes pancreatic tumorigenesis by suppressing sirtuin three via the guanine nucleotide exchange factor RCC1
doi: 10.1016/j.jbc.2025.111057
Figure Lengend Snippet: SIRT3 is transcriptionally down-regulated by KRAS G12D . A, differential gene expression of nicotinate and nicotinamide metabolism pathways. B, SIRT3 mRNA levels of HPNE cells with KRAS/Off or KRAS/On for 3 h to 96 h. The data are presented as mean ± SD ( n = 3). p values were determined by Student’s t test. ∗∗∗, p < 0.001; ∗∗∗∗, p < 0.0001. C, SIRT3 and KRAS protein levels in HPNE cells with KRAS/Off or KRAS/On for 3 h to 96 h. Cell extracts were analyzed by Western blotting using tubulin as the loading control. Note that the images of KRAS and tubulin bands were derived from the same source images shown in , C and D , as they were from the same experiment. D, effect of SCH772984 on expression of ERK1/2, phosphorylated ERK1/2, and SIRT3 protein levels in KRAS/On HPNE cells. Cells were treated with SCH772984 at indicated concentrations for 24 h. Cell extracts were analyzed by Western blotting using vinculin as the loading control. HPNE KRAS/Off cell extracts were used for comparison. E, effect of SCH772984 on expression of ERK1/2, phosphorylated ERK1/2, and SIRT3 protein levels in KRAS/On HEK293 cells. Cells were treated with SCH772984 at indicated concentrations for 24 h. Cell extracts were analyzed by Western blotting using vinculin as the loading control. HEK293 KRAS/Off cell extracts were used for comparison. F, schematic illustration of the promoter activity assay to identify potential KRAS regulated region in the SIRT3 promoter. G, activity of truncated SIRT3 promoters in HPNE KRAS/Off and HPNE KRAS/On (12 h) cells. The data are presented as mean ± SD ( n = 3). p values were determined by Student’s t test. ∗, p < 0.05;∗∗, p < 0.01. HPNE: human pancreatic normal epithelial cell.
Article Snippet: The
Techniques: Gene Expression, Western Blot, Control, Derivative Assay, Expressing, Comparison, Activity Assay