| Gene name: | SETD8 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | PC-3 |
| Experiment: | Knockdown//Flow cytometry//SA-β-gal activity assay |
| Description: | In PC3 cells harboring SETD8-specific siRNAs,we detected a greater extent of β-gal-positive staining,cell proliferation arrest,nuclear area enlargement,G2/M arrest .Consistent with its known pro-proliferation role,overexpression of SETD8 in the absence of dox treatment elevated the rate of cell growth.In dox-treated cultures undergoing senescence,introduction of ectopic SETD8 lessened cellular senescence induction to a large extent, as evidenced by the reversal of β-gal-positive staining,cell proliferation arrest,and upregulation of senescence markers p21,IL-6,andIL-8. |
| Target gene: | PPARC//P21 |
| Official symbol(s): | PPARC//P21 |
| R-AG-Target gene: | --//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | qRT-PCR//SA-β-gal activity assay//CHIP//Flow cytometry |
| Target gene description: | In support of its role as an upstream regulator, ectopic overexpression of PPARc led to an increase in the expression of SETD8 and H4K20me1, and conversely a decline in the p21 mRNA levels.To further demonstrate the role of PPARc in controlling senescence, we showed that overexpression of PPARc alleviated the extent of dox-induced cellular senescence, in terms of β-gal-positive staining , cell proliferation arrest, and SASP marker induction. Via ChIP-qPCR assay on the PPARc-overexpressing cells, we consequently found that the chromatin binding of PPARc increases on SETD8 promoter upon ectopic expression.Although RNAi-mediated abrogation SETD8 in cycling cell expectedly induced cellular senescence, based on the proportions of β-gal-positive cells and G2/M cells, simultaneous depletion of p21 notably suppressed these phenotypes. Further in line with this possible functional antagonism, concurrent depletion of p21 and SETD8 also lessened the progressive cell proliferation stall and nuclei enlargement, as compared with cells with down-regulated SETD8 only. |
| Regulatory pathway: | -- |
| R-AG-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation:
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