MicroRNA-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4

Abstract

Osteosarcoma is the most prevalent primary bone malignancy in adolescents, and ferroptosis is implicated in its pathogenesis. MicroRNA (miR)-1287-5p plays critical roles in multiple human cancers, and the present study aims to investigate the role and underlying mechanisms of miR-1287-5p in regulating ferroptosis and osteosarcoma progression. Human osteosarcoma cell lines were treated with the mimic, inhibitor or matched controls of miR-1287-5p. Cell viability, colony formation, cell death ratio and ferroptosis were determined. miR-1287-5p expression was downregulated in human osteosarcoma, but upregulated upon ferroptotic stimulation. Overexpression of miR-1287-5p significantly induced, while inhibition of miR-1287-5p suppressed ferroptosis of osteosarcoma cells, thereby modulating cell viability and colony formation. Mechanistic studies indicated that miR-1287-5p directly bound to the 3′-untranslated region of glutathione peroxidase 4 (GPX4) to inhibit its protein level and activity, and that GPX4 overexpression completely abolished the miR-1287-5p mimic-mediated ferroptotic induction and tumor suppression. Moreover, the miR-1287-5p mimic dramatically sensitized human osteosarcoma cells to cisplatin chemotherapy. Our findings prove that miR-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4, identifying an adjuvant and even alternative method for the treatment of human osteosarcoma.

Keywords:

• Osteosarcoma
• miRNA-1287-5p
• ferroptosis
• GPX4

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data that support the findings in this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81802050] and the Science and Technology Innovation Joint Fund project of Fujian Province [No. 2019Y9018].