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Updated: Jun 18, 2025

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
Published on: February 1, 2020
FOXM1 mediates methotrexate resistance in osteosarcoma cells by promoting autophagy
Luoyang Wang1, Dongchang Zhai2, Lei Tang2
1Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.
Abstract:
Osteosarcoma (OS) is a primary bone cancer mostly found in adolescents and elderly individuals. The treatment of OS is still largely dependent on traditional chemotherapy. However, the high incidence of drug resistance remains one of the greatest impediments to limiting improvements in OS treatment. Recent findings have indicated that the transcription factor FOXM1 plays an important role in various cancer-related events, especially drug resistance. However, the possible role of FOXM1 in the resistance of OS to methotrexate (MTX) remains to be explored. Here, we find that FOXM1, which confers resistance to MTX, is highly expressed in OS tissues and MTX-resistant cells. FOXM1 overexpression promotes MTX resistance by enhancing autophagy in an HMMR/ATG7-dependent manner. Importantly, silencing of FOXM1 or inhibiting autophagy reverses drug resistance. These findings demonstrate a new mechanism for FOXM1-induced MTX resistance and provide a promising target for improving OS chemotherapy outcomes.
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