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Background and aim <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月1日

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  • Jian Lu,
  • Hou Ren,
  • Wenxiao Song,
  • Shishun Xie,
  • Xiangjun Li

摘要

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.