Zhao HY, Yu CY, Ye XT, Qian ST, Huang Y, Liu QS. Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment. World J Clin Oncol 2025; 16(12): 111175 [DOI: 10.5306/wjco.v16.i12.111175]
Corresponding Author of This Article
Qing-Sheng Liu, Chief Physician, Department of Gastroenterology, Third People's Hospital of Hangzhou, No. 453 Stadium Road, Hangzhou 310009, Zhejiang Province, China. 7394822@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 24, 2025 (publication date) through Dec 30, 2025
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World Journal of Clinical Oncology
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2218-4333
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Zhao HY, Yu CY, Ye XT, Qian ST, Huang Y, Liu QS. Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment. World J Clin Oncol 2025; 16(12): 111175 [DOI: 10.5306/wjco.v16.i12.111175]
World J Clin Oncol. Dec 24, 2025; 16(12): 111175 Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.111175
Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment
Hao-Yu Zhao, Chu-Ying Yu, Xin-Tong Ye, Su-Ting Qian, Ye Huang, Qing-Sheng Liu
Hao-Yu Zhao, Chu-Ying Yu, Xin-Tong Ye, Su-Ting Qian, Hangzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
Ye Huang, Department of Gastroenterology, The Integrated Traditional Chinese and Western Medicine Hospital of Shinan District (The People's Hospital of Shinan District), Qingdao 2666071, Shandong Province, China
Qing-Sheng Liu, Department of Gastroenterology, Third People's Hospital of Hangzhou, Hangzhou 310009, Zhejiang Province, China
Co-corresponding authors: Ye Huang and Qing-Sheng Liu.
Author contributions: Zhao HY conducted the literature review on sirtuin 3 structure and its role in mitochondrial metabolism, drafted sections on biological properties of sirtuin 3, and revised the manuscript; Yu CY and Ye XT investigated the clinical translation potential of sirtuin 3, summarized studies on sirtuin 3 combined with chemotherapeutics and targeted therapies; Qian ST, Huang Y, and Liu QS conceived the review framework, supervised the overall research direction, coordinated contributions from all authors, and finalized the manuscript; Huang Y and Liu QS have played important and indispensable roles in the review framework and overall research direction as the co-corresponding authors.
Conflict-of-interest statement: The authors declare no competing interests.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing-Sheng Liu, Chief Physician, Department of Gastroenterology, Third People's Hospital of Hangzhou, No. 453 Stadium Road, Hangzhou 310009, Zhejiang Province, China. 7394822@qq.com
Received: June 26, 2025 Revised: August 14, 2025 Accepted: November 13, 2025 Published online: December 24, 2025 Processing time: 180 Days and 14.9 Hours
Abstract
Sirtuin 3 (SIRT3) is a primary mitochondrial deacetylase. Studies have confirmed that it directly activates mitophagy by modulating mitochondrial protein acetylation. As a key homeostatic mechanism, mitophagy activation alleviates oxidative stress-induced imbalance between cell proliferation and apoptosis, corrects stress-driven mitochondrial metabolic dysfunction, and thus inhibits excessive tumor growth, exerting significant antitumor effects. These functions establish SIRT3 as a key target for regulating mitophagy and cancer therapy. Clinically, strategies centered on its precise regulation may offer a novel direction for gastric cancer (GC) prevention and treatment, with selective activation remaining a critical challenge. SIRT3 could also serve as an auxiliary indicator in clinical guidelines for assessing tumor progression. Given this potential, this mini-review systematically examines SIRT3’s mechanisms in regulating mitophagy, its role in GC pathogenesis, and translational prospects for targeting SIRT3 in GC management.
Core Tip: Sirtuin 3 (SIRT3), a mitochondrial NAD+-dependent deacetylase, regulates mitophagy via protein acetylation and signaling pathways. Downregulated in gastric cancer (GC), its low expression links to poor prognosis, deeper invasion, and reduced differentiation. SIRT3 enhances mitophagy to alleviate oxidative stress, correct mitochondrial dysfunction, and inhibit GC. Preclinical studies show it synergizes with therapies, boosting efficacy and reducing toxicity. This mini-review covers its mechanisms, therapeutic potential, and prospects for activator/delivery system development.
