Biomolecules & Therapeutics

  • 제29권2호
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  • Pages.184-194
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  • 2021
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells

  • Zhu, Huihui (School of Life Sciences, Jilin University) ;
  • Wang, Yong (Urology Department, Jilin Province People's Hospital) ;
  • Wei, Tao (School of Life Sciences, Jilin University) ;
  • Zhao, Xiaoming (Central laboratory, China-Japan Union Hospital of Jilin University) ;
  • Li, Fuqiang (School of Pharmacy, Changchun University of Chinese Medicine) ;
  • Li, Yana (School of Life Sciences, Jilin University) ;
  • Wang, Fei (School of Life Sciences, Jilin University) ;
  • Cai, Yong (School of Life Sciences, Jilin University) ;
  • Jin, Jingji (School of Life Sciences, Jilin University)
  • 투고 : 2020.06.28
  • 심사 : 2020.08.25
  • 발행 : 2021.03.01
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초록

Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

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참고문헌

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