2. Academic Validation
  3. SIRT3 suppresses renal cancer progression by regulating IDH2 acetylation

SIRT3 suppresses renal cancer progression by regulating IDH2 acetylation

  • Sci Rep. 2026 Feb 6;16(1):7619. doi: 10.1038/s41598-026-37783-6.
Lei Li # 1 2,  Yongjiao Tian # 3,  Shu Chen 4,  Jin Yu 1 2,  Ziyu Chen 5,  Duiping Feng 1 2,  Tao Bai 6
Affiliations

Affiliations

  • 1 Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan, 030001, Shanxi Province, China.
  • 2 Shanxi Provincial Clinical Research Center for Interventional Medicine, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
  • 3 Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
  • 4 Department of Pathology, The First Clinical School of Medicine, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.
  • 5 Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 6 Department of Pathology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan, 030001, Shanxi Province, China. [email protected].
  • # Contributed equally.
PMID: 41651965 DOI: 10.1038/s41598-026-37783-6
Abstract

Metabolic reprogramming is a hallmark characteristic of renal cell carcinoma (RCC). SIRT3, a key mitochondrial deacetylase, plays a crucial role in metabolic reprogramming. However, its contribution to RCC development remains unclear. Bioinformatics analysis and immunohistochemistry results showed reduced SIRT3 expression in RCC and its correlation with RCC malignancy. SIRT3 knockdown enhanced cell proliferation and colony formation abilities, suggesting that SIRT3 suppresses RCC progression. Mechanistically, knockdown of SIRT3, increases the level of acetylation of isocitrate dehydrogenase 2 (IDH2) at lysine K413 (IDH2K413ac), which impairs its enzymatic activity, mitochondrial function and redox balance. This effect was reversed by the IDH2 acetylation-mimic mutant K413Q but not by the deacetylation-mimic mutant K413R. Honokiol (HKL), a SIRT3 Activator, inhibited RCC cell proliferation and colony formation by increasing SIRT3 levels. Our findings identify a novel mechanism by which SIRT3 suppressed RCC progression. SIRT3 acts as a promising therapeutic target for RCC, with HKL as a potential novel therapeutic agent.

Keywords

Acetylation; Honokiol; IDH2; Renal cell carcinoma; SIRT3.

Figures
Products