Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2025; 16(8): 104879
Published online Aug 15, 2025. doi: 10.4239/wjd.v16.i8.104879
Identification and mechanistic insights of ubiquitin-proteasome system and pyroptosis-related biomarkers in type 2 diabetes mellitus
Xiao-Jing Yuan, Zi-Chen Zhang, Jie Li, Shan-Dong Ye, Wan Zhou
Xiao-Jing Yuan, Zi-Chen Zhang, Shan-Dong Ye, Wan Zhou, Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
Jie Li, Department of Endocrinology, Anhui Provincial Hospital, Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
Co-first authors: Xiao-Jing Yuan and Zi-Chen Zhang.
Author contributions: Zhou W designed the researchand wrote the manuscript; Yuan XJ and Zhang ZC collected and analyzed the data, conducted the experiments and interpreted the experimental results; Yuan XJ and Li J performed the statistical analyses; Ye SD reviewed and edited the manuscript; Zhou W is the guarantor of this work; All authors read and approved the final version of the manuscript. Yuan XJ and Zhang ZC have contributed equally to this work.
Supported by National Natural Science Foundation of China, No. 82270863 and No. 82470849; Major Project of Anhui Provincial University Research Program, No. 2023AH040400; Joint Fund for Medical Artificial Intelligence, No. MAI2023Q026; and the Project of Health Commission Scientific Research in Anhui Province, No. AHWJ2024Aa20477.
Institutional review board statement: This study received approval from the Ethics Committee of The First Affiliated Hospital of USTC.
Institutional animal care and use committee statement: This study received approval from the Animal Care and Research Advisory Committee of the First Affiliated Hospital of University of Science and Technology of China.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
ARRIVE guidelines statement: This study received approval from the Animal Care and Research Advisory Committee, following ARRIVE guidelines.
Data sharing statement: The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Wan Zhou, PhD, Chief Physician, Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei 230001, Anhui Province, China. zwan@ustc.edu.cn
Received: January 5, 2025
Revised: March 23, 2025
Accepted: May 26, 2025
Published online: August 15, 2025
Processing time: 222 Days and 0.4 Hours
Core Tip

Core Tip: This study identified four ubiquitination and pyroptosis-associated biomarkers (ATP binding cassette subfamily C member 8, retinol binding protein 4, Ras protein-specific guanine nucleotide-releasing factor 1, and solute carrier family 34 member 2) in type 2 diabetes mellitus (T2DM) through integrated bioinformatics analysis, establishing a potential mechanistic link between ubiquitin-proteasome system dysregulation and pyroptosis in T2DM pathogenesis. These biomarkers were enriched in oxidative phosphorylation and mitogen-activated protein kinase signaling pathways, and modulated immune cell infiltration. Our research discovered possible drug candidates and a gene interaction network linked to RNA competition, which may aid in detecting and treating type 2 diabetes.