Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments

Sihui Chen; Yi Jiang; Guoqin Xie; Peng Wu; Jinyu Zhu

doi:10.3389/fgene.2024.1522809

Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments

Front Genet. 2025 Jan 10:15:1522809. doi: 10.3389/fgene.2024.1522809. eCollection 2024.

Authors

Sihui Chen^#^{1

2}, Yi Jiang^#^{1

2}, Guoqin Xie^{1

2}, Peng Wu^{1

2}, Jinyu Zhu^{1

2}

Affiliations

¹ Department of Orthopedics, First Hospital of Jiaxing, Jiaxing, China.
² College of Medicine, Jiaxing University, Jiaxing, China.

^# Contributed equally.

Abstract

Background: Ferroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.

Methods: Based on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.

Results: This study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.

Conclusion: The study provides a theoretical basis for the treatment of osteoporosis.

Keywords: BMSCs; KMT2D; aging; ferroptosis; osteoporosis.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by internal funding from the First Hospital of Jiaxing, China (Grant Agreement 2022-xkdtr-01, 2024-ZD-005), the Key Departments of Jiaxing, China (Grant Agreement 2023-ZC-012), the Key Laboratory Project of Jiaxing, China (Grant Agreement 2022-yzcsgtjzjz).