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Open Access 01-12-2023 | osteosarcoma | Research

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

Authors: Xujun Li, Jiangyi Liu

Published in: BMC Cancer | Issue 1/2023

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.

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Title: FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma
Authors: Xujun Li
Jiangyi Liu
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: osteosarcoma
Osteosarcoma
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-10626-7

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