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Background <p>Osteosarcoma is a common primary bone malignancy with poor prognosis. While microRNA dysregulation has been implicated in osteosarcoma progression, the role of exosome-mediated miRNAs, particularly miR-875-3p, in regulating ferroptosis and tumor progression remains unclear. This study aimed to investigate whether miR-875-3p promotes osteosarcoma proliferation, migration, and invasion by targeting SLC39A14 and inhibiting ferroptosis.</p> Methods <p>Exosomes were isolated from osteosarcoma tissues and H143B cells, then characterized by transmission electron microscopy as well as Western blot. Bioinformatics analysis and dual-luciferase assays identified SLC39A14 as a direct target of miR-875-3p. Lentiviral and adenoviral transfection were used to knockdown miR-875-3p and SLC39A14 in H143B cells. Cell viability, migration, and invasion were assessed using CCK-8, wound healing, and Transwell assays. Ferroptosis markers (GSH/GSSG, Fe²⁺, ROS, MDA) and related genes (GPX4, ACSL4, xCT) were eventually measured.</p> Results <p>Exosomes isolated from osteosarcoma tissues exhibited a typical spherical morphology and were positive for exosomal markers (HSP70, TSG101). MiR-875-3p was upregulated in osteosarcoma tissues and cell-derived exosomes, while SLC39A14 was downregulated. Knockdown of miR-875-3p upregulated SLC39A14, promoted ferroptosis, and suppressed osteosarcoma cell proliferation, migration, and invasion in vitro. In contrast, SLC39A14 knockdown attenuated ferroptosis and enhanced malignant phenotypes. In vivo, miR-875-3p knockdown inhibited tumor growth, whereas SLC39A14 knockdown promoted it.</p> Conclusion <p>miR-875-3p promotes osteosarcoma progression by targeting SLC39A14 and suppressing ferroptosis, suggesting the miR-875-3p/SLC39A14 axis as a potential therapeutic target for osteosarcoma treatment.</p>

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The role and mechanism of miR-875-3p in targeting SLC39A14 to regulate ferroptosis in osteosarcoma proliferation, migration, and invasion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月25日

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  • Jie Huang,
  • Jiaqi He,
  • Liuru Lu,
  • Chengjun Sun,
  • Yongheng Dai,
  • Zhandong Bo

摘要

Background

Osteosarcoma is a common primary bone malignancy with poor prognosis. While microRNA dysregulation has been implicated in osteosarcoma progression, the role of exosome-mediated miRNAs, particularly miR-875-3p, in regulating ferroptosis and tumor progression remains unclear. This study aimed to investigate whether miR-875-3p promotes osteosarcoma proliferation, migration, and invasion by targeting SLC39A14 and inhibiting ferroptosis.

Methods

Exosomes were isolated from osteosarcoma tissues and H143B cells, then characterized by transmission electron microscopy as well as Western blot. Bioinformatics analysis and dual-luciferase assays identified SLC39A14 as a direct target of miR-875-3p. Lentiviral and adenoviral transfection were used to knockdown miR-875-3p and SLC39A14 in H143B cells. Cell viability, migration, and invasion were assessed using CCK-8, wound healing, and Transwell assays. Ferroptosis markers (GSH/GSSG, Fe²⁺, ROS, MDA) and related genes (GPX4, ACSL4, xCT) were eventually measured.

Results

Exosomes isolated from osteosarcoma tissues exhibited a typical spherical morphology and were positive for exosomal markers (HSP70, TSG101). MiR-875-3p was upregulated in osteosarcoma tissues and cell-derived exosomes, while SLC39A14 was downregulated. Knockdown of miR-875-3p upregulated SLC39A14, promoted ferroptosis, and suppressed osteosarcoma cell proliferation, migration, and invasion in vitro. In contrast, SLC39A14 knockdown attenuated ferroptosis and enhanced malignant phenotypes. In vivo, miR-875-3p knockdown inhibited tumor growth, whereas SLC39A14 knockdown promoted it.

Conclusion

miR-875-3p promotes osteosarcoma progression by targeting SLC39A14 and suppressing ferroptosis, suggesting the miR-875-3p/SLC39A14 axis as a potential therapeutic target for osteosarcoma treatment.