The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin.

Autor: Wang XW; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China.; Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China., Guo QQ; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Yu Y; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Zhou TT; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Zhang SY; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Wang Z; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Liu JW; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Tang J; Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China., Jiang XY; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Wang SS; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Guo WD; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Xu HD; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Sun HY; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Li ZW; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Song XY; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China., Zhao JG; Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China., Cao L; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.; Key Laboratory of Liaoning Province, China Medical University, Shenyang, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2022 Jan; Vol. 26 (2), pp. 491-506. Date of Electronic Publication: 2021 Dec 06.
DOI: 10.1111/jcmm.17107
Abstrakt: In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.
(© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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