Table 2.
The role of SIRT6 in various human cancers.
| Cancer type | Function | Cell line | In vivo | Mechanism(s) |
|---|---|---|---|---|
| HCC | suppressor | HepG2 | Inhibit phosphorylation of ERK1/2.77 | |
| HepG2, HCCLM3 | Transfected HepG2 xenograft | Reduce cyclin D1 and p-ERK expression.75 | ||
| HepG2, Huh7 | FOXA2 and SIRT6 coordinately suppress the expression of ZEB2.74 | |||
| HepG2, H1299, HCT116, U2OS, 293A | Transfected HepG2 xenograft | UBE3A-mediated SIRT6 degradation promotes the proliferation.78 | ||
| oncogene | PLC/PRF/5, SMMC-7721, Huh-7, SK-Hep-1 | Transfected SK-Hep-1 xenograft | Inhibit activation of Bax by H3K9 deacetylation.79 | |
| SK-Hep-1, Huh-7 | Deacetylation of Ku70 to enhance the Ku70-Bax interaction.48 | |||
| Hep3B, Huh-7, MHcc-97H, -97l, -lM6, -lM3, YY-8103, SK-hep-1 | Upregulate Bcl-2, pERK and decrease Bax.81 | |||
| Hep3B | Hep3B xenograft | Stimulate degradation of E-cadherin.82 | ||
| HepG2, Huh7, HeLa | Regulate FoxO3 activity.84 | |||
| Hep3B, HepG2, SNU475, SK-Hep1, SNU449, Huh-7 | SIRT6-KO Hep3B xenograft | Prevent DNA damage and cellular senescence.80 | ||
| HepG2, Huh7 | HepG2 and Huh7 xenografts | Enable TGF-β1/H2O2 /HOCl.83 | ||
| Colon cancer | suppressor | HCT116, RKO | HCT116 xenograft | USP10 inhibits c-Myc through SIRT6 stabilization.87 |
| RKO, HT-29, SW620, COLO 205, HCT116 | MiR-34c-5p inhibits SIRT6 to activate JAK2/STAT3.90 | |||
| HCT116, HT29 | SW620 xenograft | Modulate PTEN/AKT signaling.89 | ||
| LoVo, HCT-116, SW48, HT-29, DLD1, SW480 | Transfected LoVo xenograft | Akt inactivation increases FoxO3a to elevate SIRT6 expression.88 | ||
| oncogene | HCT116, RCO | Promote EMT process.91 | ||
| Lung cancer | suppressor | A549 | SIRT6 plays radiosensitization effect on A549 cells.99 | |
| NCI-H1299, HCC827, A549 | Astragaloside IV sensitizes tumor cells to gefitinib via regulation of SIRT6.100 | |||
| A549 | Inhibit Twist1 expression.96 | |||
| A549 | Decrease expression of PKM, LDHA, and HK.98 | |||
| A549 | Transfected A549 xenograft | Inhibits HIF1α expression.97 | ||
| oncogene | A549, SPC-A1, GLC82, PC9 | Activate ERK1/2/MMP9 pathway.102 | ||
| A549 and H1299 | Drive EMT via transrepression of KLF4.104 | |||
| A549 | transfected A549 xenograft | MiR-186 inhibits SIRT6 to antagonize cancer progression.103 | ||
| Breast cancer | suppressor | MCF-7, MDA-MB-231 | MDA-MB-231 xenografts and orthotopic model | AKT phosphorylate SIRT6 to induce MDM2-mediated degradation.106 |
| MCF7, Hs578t | RUNX2-mediated repression of the SIRT6 regulates metabolic pathways.105 | |||
| oncogene | MCF-7 | Decrease FoxO acetylation and expression.109 | ||
| BT474, BT474-LapR | Regulate FoxO3 acetylation and lapatinib sensitivity.108 | |||
| MCF7, T47D, MDA-MB231, 293 | CSNK2A1 mediates phosphorylation of SIRT6.107 | |||
| Glioma | suppressor | T98G, U87MG, A172, U251, CCF-STTG1 | Suppress expression of RNA-binding protein PCBP2.115 | |
| U87-MG, T98G | Inhibit JAK2/STAT3 signaling pathway.112 | |||
| U87, T98, A172, U251 | MiR-33a suppresses SIRT6 facilitates tumor growth through apoptosis and oxidative stress resistance.113 | |||
| U251, U87, LN18, A172 | Downregulate NOTCH3 expression.110 | |||
| U251, U87 | Transfected U87 xenograft | FoxO3a upregulates SIRT6 to inhibit Warburg effect.114 | ||
| A-172, U-138 MG, U-251 MG | MST1 upregulates SIRT6 expression via FoxO3a.111 | |||
| Bone cancer | suppressor | SAOS-2, MG-63 | Downregulate N-cadherin.118 | |
| U2OS, MG-63 | FoxN3 transcriptionally regulates SIRT6, suppresses cancer migration and invasion.119 | |||
| U2-OS, MG-63 | Transfected U2-OS xenograft | MiR-654–5p inhibits tumor growth and represses SIRT6 expression.120 | ||
| oncogene | NCI-H929, U266, KMS-28, RPMI-8226/S, MM.1S | Transfected NCI-H929 xenografts | Inhibit MAPK pathway signaling via H3K9 deacetylation.116 | |
| U2OS, MG-63, Saos-2, 143B | Regulate ERK1/2/MMP9 pathway.117 | |||
| Skin Cancer | suppressor | SKMel-239, 501Mel, Mel888, SKMel-147, STCs, SKMel-28 | L-C-B, S6.2–7, and S4.1–1 xenografts | SIRT6 inhibition activates IGF-AKT to promote melanoma drug resistance.125 |
| MV3 | Transfected MV3 xenograft | FoxO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma.126 | ||
| oncogene | NHEK | SIRT6-WT and skin-specific homozygous SIRT6-KO mice | Repress AMPK signaling to promote COX-2 expression.121 | |
| A375, Hs 294T | SIRT6-KD induces G1-phase arrest and increase senescence-like type.122 | |||
| HKC, SCC13 | Sirt6 down-regulation reproduces the miR-34a pro-differentiation effects.127 | |||
| Cervical carcinoma | suppressor | HeLa | Driving apoptosis is mediated by activation p53 and p73 apoptotic signaling cascades.59 | |
| Fibrosarcoma | suppressor | HT1080 | Driving apoptosis is mediated by activation p53 and p73 apoptotic signaling cascades.59 | |
| Nasopharyngeal carcinoma | suppressor | 5–8 F, CNE1 | Inhibit NF-κB to induce apoptosis.128 | |
| Renal cancer | oncogene | 786-O | SIRT6 silence in RCC leads to G1/S phase arrest.129 | |
| Prostate cancer | oncogene | PC-3, DU145, 22RV1, LNCaP | SIRT6 knockdown leads to cell cycle arrest, increases apoptosis and DNA damage.130 | |
| Ovarian cancer | suppressor | SKOV3, OVCAR3 | Downregulate Notch 3 expression.132 | |
| oncogene | OVCAR3, OVCAR5 | Active β-catenin and increase EMT.133 | ||
| Pancreatic Cancer | suppressor | Panc-1, BxPc3, YAPC, ASPC-1, SW1990, psn1 | PDAC xenograft | SIRT6 regulates Lin28b through promoting histone deacetylation.131 |
| Leukemia | suppressor | Jurkat cells, RS4:11 | SIRT6-PARP1 affects HMGB1 polyADP-ribosylation and acetylation and promotes chemotherapy-induced autophagy.137 | |
| oncogene | U937, MOLM-14, MV4–11, HL60, HEL, THP-1, NOMO-1, OCI-AML2, OCI-AML3, NB4 | SIRT6-depleted xenograft | Depletion of SIRT6 enzymatic activity increases AMLcells’ vulnerability to DNA-damaging agents.134 |