Related Experiment Video
Updated: Nov 14, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
KDM4A-mediated histone demethylation of SLC7A11 inhibits cell ferroptosis in osteosarcoma
Meng Chen1, Yuhang Jiang2, Yangbai Sun2
1Department of Orthopedics, Trauma Centre of Fujian, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Abstract:
Osteosarcoma (OS) is the most common type of bone tumor that seriously affects limb function and induces great pain in patients. Lung metastasis and chemotherapy resistance are two key issues leading to the poor prognosis of OS patients, therefore new treatment targets and strategies are urgently needed. In our study, we uncovered the role of histone demethylase KDM4A in regulating OS cell ferroptosis and tumor progression. KDM4A was significantly upregulated in OS specimens and high KDM4A expression was associated with poorer prognosis in OS patients. Our data indicated that targeting KDM4A significantly increased OS cell death, enhanced cisplatin response, and attenuated migration ability in vitro. KDM4A depletion dramatically inhibited tumor progression and lung metastasis of OS in vivo Further experiments confirmed that KDM4A knockdown promoted OS cell ferroptosis, a special non-apoptotic form of cell death. KDM4A regulates SLC7A11 transcription and OS cell ferroptosis by controlling H3K9me3 demethylation in the promoter region of SLC7A11. Our findings deepened the recognition of epigenetic regulatory mechanism in OS tumorigenesis, chemoresistance, and metastasis, suggesting that KDM4A activity may be a potential therapeutic target for future OS treatment.
Insights
Targeting KDM4A, a histone demethylase, inhibits osteosarcoma progression and metastasis by promoting ferroptosis. This epigenetic regulation offers a new therapeutic strategy for bone cancer patients.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Osteosarcoma (OS) is a primary bone cancer with poor prognosis due to metastasis and chemotherapy resistance.
- Novel therapeutic targets are crucial for improving outcomes in osteosarcoma patients.
Purpose of the Study:
- To investigate the role of histone demethylase KDM4A in osteosarcoma progression, ferroptosis, and chemoresistance.
- To evaluate KDM4A as a potential therapeutic target for osteosarcoma.
Main Methods:
- Analysis of KDM4A expression in osteosarcoma specimens.
- In vitro and in vivo experiments involving KDM4A knockdown.
- Assessment of cell death, cisplatin response, migration, tumor progression, and lung metastasis.
- Investigation of KDM4A's epigenetic regulation of SLC7A11 and ferroptosis.
Main Results:
- KDM4A was upregulated in osteosarcoma and associated with poor prognosis.
- KDM4A inhibition increased cell death, enhanced cisplatin sensitivity, and reduced migration in vitro.
- KDM4A depletion suppressed tumor growth and lung metastasis in vivo.
- KDM4A knockdown promoted osteosarcoma cell ferroptosis by regulating SLC7A11 transcription via H3K9me3 demethylation.
Conclusions:
- KDM4A plays a significant role in osteosarcoma tumorigenesis, chemoresistance, and metastasis.
- Targeting KDM4A promotes ferroptosis and represents a promising therapeutic strategy for osteosarcoma.
