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.
Data availability
All raw data are available from the corresponding author upon request via email at Baitao-sxmu@hotmail.com.
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Funding
This work was supported by the Shanxi Provincial Clinical Research Center for Interventional Medicine, No. 202204010501004.
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Conceptualization: LL. Investigation: LL, TB. Validation: LL, YJ, JY, SC, DP, ZY. Methodology: LL, YJ, SC, TB. Data curation: LL, YJ, SC. Visualization: LL, YJ, JY, DP. Writing—original draft: LL. Writing—review & editing: YJ, ZY, TB. Resources: TB. Formal analysis: TB. Project administration: TB. Supervision: TB. All authors read and approved the final manuscript.
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The use of RCC tissues for research purposes was approved by the Ethics Committee of Beijing Friendship Hospital (No: BJFH-EC-S/2013–006). The clinical study conformed to the standard set by the Declaration of Helsinki.
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Li, L., Tian, Y., Chen, S. et al. SIRT3 suppresses renal cancer progression by regulating IDH2 acetylation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37783-6
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DOI: https://doi.org/10.1038/s41598-026-37783-6
