ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Protein Biochemistry for Basic and Applied Sciences
This article is part of the Research TopicMicroenvironmental Control of Cancer Development and Therapy ResistanceView all articles
Exploring hub genes related to adipocytokines in keloids: A combined analysis integrating single-cell, Mendelian randomization and bulk transcriptome data with experimental verification
Provisionally accepted
- People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Keloids are fibroproliferative skin tumors with excessive collagen deposition and are strongly linked to adipocytokine dysregulation. However, the underlying mechanisms remain unclear. This study aimed to identify potential therapeutic targets and elucidate adipocytokine-related pathological mechanisms underlying keloid formation. Methods: Hub genes were identified using differential expression analysis and machine learning. Mendelian randomization assessed causal relationships. Functional insights were gained through gene set enrichment analysis (GSEA) and drug prediction. Single-cell RNA sequencing (scRNA-seq) identified key cell types, and RT-qPCR validated gene expression. Results: We identified 818 differentially expressed genes, narrowing to seven key genes and two hub genes: PIK3R3 and ANGPTL5. MR indicated PIK3R3 as a causal risk factor for keloids, while ANGPTL5 showed no causal association. GSEA linked PIK3R3 to the TEL pathway and ANGPTL5 to adipocyte differentiation. Drug predictions included harmine for PIK3R3 and silica for ANGPTL5. scRNA-seq highlighted fibroblasts as key cells expressing these genes. RT-qPCR confirmed PIK3R3 upregulation in keloids, though ANGPTL5 results were inconsistent, possibly due to sample limitations. Conclusions: This study, based on the integrated re-analysis of existing publicly available transcriptomic data and combined with clinical sample validation, revealed the potential hub roles of PIK3R3 and ANGPTL5 in keloid pathogenesis. PIK3R3 was validated as a causal hub gene, while ANGPTL5 also showed relevance. The study provides new molecular evidence and mechanistic insights for understanding the adipocytokine-related pathological mechanisms of keloids, and suggests potential therapeutic directions such as harmine for future research.
Keywords: Adipocytokine, Hub genes, Keloids, Mendelian Randomization Analysis, single-cellanalysis
Received: 06 Nov 2025; Accepted: 05 Feb 2026.
Copyright: © 2026 Mahemuti, Chen, Li and Yilihamu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alimire Yilihamu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.