Page 68 - D. Cancer biology

[D. Cancer biology-48]

A Sirt7-Dependent Deacetylation Modulates DNA Damage Repair

and Loss-of-Hepatic Sirt7 Promotes Hepatocellular Carcinoma

Yun A Kim¹, Baeki E Kang¹, Johan Auwex², Dongryeol Ryu¹

¹Department of Mol. Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea,

²Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne
1015, Switzerland

Sirtuin 7 (Sirt7) is one of seven mammalian NAD+-dependent protein deacylases and is also known as a nuclear

sirtuin together with Sirt1 and Sirt6. Although growing evidence shows Sirt7 has diverse roles in cells, the in vivo

function of Sirt7 is only understood partially, so far. Early studies proposed Sirt7 as an oncogenic factor promoting
oncogenic transformation, however recent studies demonstrate Sirt7 is crucial for DNA repair and genomic stability.
Here we report loss-of-hepatic Sirt7 Promotes hepatocellular carcinoma in a DEN-induced DNA damage mouse

model. We observed bigger and more hepatic tumor colonies from the micro-computed tomography (micro-CT) of
Diethylnitrosamine (DEN)-injected Sirt7Hep-/- liver. Furthermore, liver histology, qRT-PCR, and immunoblotting

assays revealed the typical feature of hepatic cancer including increased hepatic Alpha-Fetoprotein (Afp), Ki67,
Kitl/Scf, Vgef, and Pcna. In serum, we also found increased several cytokines including IL-6, TNFα, and AFP, which

are well-established HCC markers. Our study demonstrates hepatic loss-of-Sirt7 promotes hepatocellular
carcinogenesis unlike the early studies described Sirt7 as an oncogenic factor.