A novel ferroptosis-related microRNA signature with prognostic value in osteosarcoma: Ferroptosis-related microRNA signature in osteosarcoma

• Published in: Acta biochimica et biophysica Sinica 2023-10, Vol.55 (11), p.1758-1769
• Main Authors: Shao, Jie, Zhang, Yi, Chang, Zhu, Du, Shiyao, Li, Wei, Bai, Yushu, Lu, Chunwen, Xu, Tianming
• Format: Article
• Language: English
• ISSN: 1672-9145; 1745-7270
• DOI: 10.3724/abbs.2023236

The induction of ferroptosis is suggested to be a potential therapeutic strategy for cancers. MicroRNAs (miRNAs) are reported to play an important role in cell death processes. This study aims to construct and validate a risk model based on ferroptosis-related miRNAs (FR_miRNAs) to predict prognosis and identify novel therapeutic targets for osteosarcoma. Data from the Therapeutically Applicable Research to Generate Effective Treatments database are used as the training cohort. A prognostic signature based on two FR_miRNAs (miR-635 and miR-593) is developed using univariate Cox regression, least absolute shrinkage and selection operator regression, and multivariate Cox regression analyses. The area under the curve values of the prognostic signature to predict the 1-year, 2-year, 3-year, and 5-year overall survival rates in patients with osteosarcoma are 0.782, 0.781, 0.722, and 0.777, respectively, indicating a good predictive ability. Based on the risk score, patients are divided into low-risk and high-risk groups. Patients with high-risk scores are associated with poor survival. The risk level is determined to be an independent prognostic factor. A nomogram is established for predicting prognosis. The expression levels of PRNP (miR-635-related ferroptosis-related gene (FRG); P =0.024) and HILPDA (miR-593-related FRG; P =0.025) are significantly different between the low-risk and high-risk groups. All results are validated in an external cohort (GSE39040). The results of the functional assay reveal that miR-635 mimics inhibit osteosarcoma (OS) cell proliferation and migration, whereas miR-593 overexpression exerts the opposite effect. In conclusion, miR-635 and miR-593 exert contrasting regulatory effects on OS cell proliferation and migration.