Table 2.
Mechanistic Roles of Sirtuins (SIRT1–7) in Prostate Cancer.
| Sirtuins | Mechanism/Target | Function | References |
|---|---|---|---|
| SIRT1 | Deacetylates and upregulates Matrix Metalloproteinase-2 (MMP2) expression | Promotes prostate cancer cell invasion | [83] |
| SIRT1 | Downregulates EMT-related protein (E-cadherin) and upregulates mesenchymal markers (vimentin and N-cadherin) | Promotes movement, migration, and invasion of prostate cancer cells | [84] |
| SIRT1 | Downregulates expression of epithelial marker (E-cadherin) and upregulates expression of mesenchymal markers (N-cadherin and fibronectin) and EMT-inducing transcription factor (ZEB1) | Promotes migration and metastasis of prostate cancer | [85] |
| SIRT1 | Deacetylates and deactivates p53 and FOXO1 | Promotes development of prostate cancer | [86] |
| SIRT1 | Upregulates phosphorylation of S6K and 4EBP1 | Suppresses cell proliferation and induces autophagy of prostate cancer | [87] |
| SIRT1 | Antagonizes PCAF-catalyzed MPP8-K439 acetylation | Promotes migration, invasion, and EMT of prostate cancer | [88] |
| SIRT1 | Deacetylates AR and histone H3, and suppresses AR-mediated gene transcription | Inhibits proliferation of prostate cancer | [89] |
| SIRT1 | Deacetylates AR and inhibits coactivator-induced interactions between AR amino and carboxyl termini | Inhibits proliferation of prostate cancer | [90] |
| SIRT1 | Upregulates AR signaling | Promotes progression of prostate cancer | [91] |
| SIRT2 | Not known | Not Known | Not Known |
| SIRT3 | Inhibits phosphorylation of Akt, leading to ubiquitination and degradation of oncoprotein c-Myc | Inhibits proliferation of prostate cancer | [92] |
| SIRT3 | Promotes FOXO3A expression by suppressing Wnt/β-catenin pathway; Downregulates EMT | Inhibits migration and metastasis of prostate cancer | [93] |
| SIRT2 | Not known | Not Known | Not Known |
| SIRT3 | Inhibits phosphorylation of Akt, leading to ubiquitination and degradation of oncoprotein c-Myc | Inhibits proliferation of prostate cancer | [92] |
| SIRT3 | Promotes FOXO3A expression by suppressing Wnt/β-catenin pathway; Downregulates EMT | Inhibits migration and metastasis of prostate cancer | [93] |
| SIRT3 | Inhibits cleavage of poly (ADP-ribose) polymerase (PARP) and upregulates expression of proliferating cell nuclear antigen | Promotes proliferation and suppresses apoptosis of prostate cancer | [94] |
| SIRT3 | Reduces the level of acetylated mitochondrial ACO2 | Reduces growth and survival of prostate cancer | [95] |
| SIRT3 | Inhibits RIPK3-mediated necroptosis and innate immune response | Promotes progression of prostate cancer | [96] |
| SIRT4 | Decreases glutamine uptake and metabolism | Inhibits proliferation of prostate cancer | [97] |
| SIRT4 | Deacetylates ANT2 to promote its ubiquitination and degradation | Suppresses proliferation and promotes mitochondrial-mediated apoptosis of prostate cancer | [98] |
| SIRT5 | Upregulates cyclin D1, MMP9, and MAPK signaling proteins; downregulates ACAT1 protein expression | Promotes proliferation, invasion, and migration of prostate cancer |
[99] |
| SIRT5 | Inhibits the PI3K/AKT signaling | Suppresses growth and metastasis of prostate cancer | [100] |
| SIRT5 | Desuccinylates LDHA | Reduces migration and invasion of prostate cancer | [101] |
| SIRT6 | Increases Bcl-2 gene expression and induces cell cycle arrest at the sub-G1 phase | Inhibits apoptosis and promotes survival and proliferation of prostate cancer | [102] |
| SIRT6 | Downregulates E-cadherin level and upregulates N-cadherin level | Promotes migration and invasion of prostate cancer | [103] |
| SIRT6 | Inhibits RIPK3-mediated necroptosis and innate immune response | Promotes progression of prostate cancer | [96] |
| SIRT6 | Upregulates the Wnt/β-catenin signaling | Promotes progression of prostate cancer | [104] |
| SIRT7 | Upregulates expression of EMT marker (fibronectin) | Promotes aggressiveness of prostate cancer | [105] |
| SIRT7 | Upregulates AR signaling, LC3BI to LC3BII conversion, vimentin, slug, MMP2, and MMP9; downregulates SMAD4 protein expression | Promotes cell proliferation, metastasis, and androgen-induced autophagy of prostate cancer | [106] |
| SIRT7 | Downregulates EMT-related protein (E-cadherin) and upregulates mesenchymal markers (vimentin) and slug | Promotes migration and metastasis of prostate cancer | [107] |