miR-155-5p promotes osteosarcoma progression and cisplatin resistance by targeting the SOCS1/STAT1/c-Fos signaling axis

BACKGROUND AND AIM: Osteosarcoma remains challenging to treat due to metastasis and chemoresistance. This study investigated the role and mechanisms of miR-155-5p in osteosarcoma progression and chemoresistance. METHODS: We analyzed miR-155-5p expression in clinical datasets and evaluated its biological functions in osteosarcoma cell lines through proliferation, migration, and apoptosis assays. Target identification and validation were performed using bioinformatics analysis, dual-luciferase reporter assays, and molecular studies. Cisplatin-resistant cells were used to examine chemoresistance mechanisms. RESULTS: Elevated miR-155-5p expression correlated with poor survival in patients and was significantly upregulated in osteosarcoma. miR-155-5p promoted proliferation and migration while inhibiting apoptosis across multiple cell lines. Mechanistically, miR-155-5p directly targeted SOCS1, leading to decreased STAT1 and increased c-Fos expression. This axis modulated downstream effectors including P-glycoprotein, Bcl-2, and Bax. In cisplatin-resistant cells, dysregulation of the miR-155-5p/SOCS1 axis contributed to drug resistance. CONCLUSIONS: miR-155-5p functions as an oncogenic microRNA by targeting the SOCS1/STAT1/c-Fos axis, promoting malignant behaviors and chemoresistance in osteosarcoma. This pathway represents a potential therapeutic target.