Apigenin Suppresses Bladder Cancer via the SIRT6-NCOA2-PPARα Axis

International Journal of Biological Sciences 2026 Open access

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Authors: Ying Liu, Zhen-Duo Shi, Yun-Fei Wei, Si-Yuan Jiang, Harsh Patel, Qian-Zi LIU, Yang Dong, Yi-Fang Liu, Lin Hao, Shan Gao, Dong-Hua Yang, Qiang Li
+1 more Cong-Hui Han
DOI: 10.7150/ijbs.128177
Cited by: 0

Abstract

functional assays and dynamic xenograft models. Mechanistically, we applied an integrated multi-omics approach to unravel that apigenin enhances SIRT6-mediated deacetylation of Nuclear Receptor Coactivator 2 (NCOA2), leading to site-specific deacetylation of NCOA2 at lysine 780 and 785. This modification potentiates PPARα transcriptional activity, reprograms cellular energy metabolism, and disrupts mitochondrial membrane potential. Clinically, reduced SIRT6 expression coupled with elevated NCOA2 and mitochondrial/β-oxidation markers correlates with metastatic progression in bladder cancer. Together, these findings identify a previously unrecognized SIRT6-NCOA2-PPARα signaling axis as a metabolic vulnerability in bladder cancer.

Fields of Study & Subjects

Sirtuins and Resveratrol in Medicine Bladder and Urothelial Cancer Treatments Flavonoids in Medical Research

Publication details

Journal / source
International Journal of Biological Sciences
Volume
22
Issue
6
Pages
3070–3086
Publication date
26 February 2026
Language
EN