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.

中文翻译：

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一种与铁死亡相关的新型 microRNA 特征，在骨肉瘤中具有预后价值。

铁死亡的诱导被认为是癌症的潜在治疗策略。据报道，MicroRNA (miRNA) 在细胞死亡过程中发挥着重要作用。本研究旨在构建并验证基于铁死亡相关 miRNA（FR_miRNA）的风险模型，以预测骨肉瘤的预后并确定新的治疗靶点。来自治疗适用研究以产生有效治疗数据库的数据被用作训练队列。使用单变量 Cox 回归、最小绝对收缩和选择算子回归以及多变量 Cox 回归分析开发基于两种 FR_miRNA（miR-635 和 miR-593）的预后特征。预测骨肉瘤患者 1 年、2 年、3 年和 5 年总生存率的预后特征曲线下面积值分别为 0.782、0.781、0.722 和 0.777，表明良好的预测能力。根据风险评分，将患者分为低风险组和高风险组。高风险评分的患者与较差的生存率相关。风险水平被确定为独立的预后因素。建立列线图来预测预后。PRNP（miR-635相关的铁死亡相关基因（FRG）；P=0.024）和HILPDA（miR-593相关的FRG；P=0.025）的表达水平在低危组和高危组之间存在显着差异。 。所有结果均在外部队列 (GSE39040) 中得到验证。功能测定结果表明，miR-635 模拟物抑制骨肉瘤 (OS) 细胞增殖和迁移，而 miR-593 过表达则发挥相反的作用。总之，miR-635 和 miR-593 对 OS 细胞增殖和迁移发挥不同的调节作用。