FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma.

Abstract

BACKGROUND:

This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on the regulation of ferroptosis in osteosarcoma progression.

METHODS:

The function of FANCD2 on cell viability, invasion, migration, and tumor growth were explored. FANCD2 and pathway-related genes were determined by western blot. Ferroptosis-associated markers were determined, including lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe2+), and ferroptosis-related genes.

RESULTS:

FANCD2 expression was increased in osteosarcoma cells. FANCD2 knockdown reduced cell viability, invasion, and migration of osteosarcoma cells. FANCD2 knockdown regulated ferroptosis-related gene expression, and distinctly increased the levels of LIP, Fe2+, and lipid peroxidation, and these effects were reversed by a ferroptosis inhibitor Fer-1. In addition, JAK2 and STAT3 expression were reduced by silencing of FANCD2, and STAT3 activator (colivelin) distinctly reversed tumor suppressor effects of FANCD2 silencing on osteosarcoma development.

CONCLUSION:

These findings suggested that FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. These findings may provide novel therapeutic ideas for clinical treatment of osteosarcoma.

• Authors: Xujun Li, Jiangyi Liu
• Journal: BMC cancer (BMC Cancer) Vol. 23 Issue 1 Pg. 179 (Feb 22 2023) ISSN: 1471-2407 [Electronic] England
• PMID: 36814203 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• FANCD2 protein, human
• Fanconi Anemia Complementation Group D2 Protein
• Iron
• JAK2 protein, human
• Janus Kinase 2
• STAT3 protein, human
• STAT3 Transcription Factor

Topics

• Humans
• Bone Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Fanconi Anemia Complementation Group D2 Protein (metabolism)
• Ferroptosis
• Iron (pharmacology)
• Janus Kinase 2 (metabolism)
• Osteosarcoma (metabolism)
• STAT3 Transcription Factor (metabolism)