BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair

  • Yuna Kim (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Baeki E. Kang (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Karim Gariani (Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals) ;
  • Joanna Gariani (Department of Radiology, Hirslanden Grangettes Clinic) ;
  • Junguee Lee (Department of Pathology, Konyang University) ;
  • Hyun-Jin Kim (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Chang-Woo Lee (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Kristina Schoonjans (Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne) ;
  • Johan Auwerx (Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne) ;
  • Dongryeol Ryu (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine)
  • 투고 : 2023.10.09
  • 심사 : 2023.12.07
  • 발행 : 2024.02.29
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초록

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

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과제정보

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2021R1A6A 3A13044725 to Y.K.; 2020R1A2C2010964, 2022K2A9A1A06 091879, 2023R1A2C3006220, RS-2023-00283539, and RS-2023-00261370 to D.R.). D.R. was supported by a "GIST Research Institute (GRI) IIBR" grant funded by the GIST in 2023.

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