Cell death pathways related to ferroptosis are implicated in the progression of melanoma. Emerging data reporting the upregulation of microRNA (miR)-130b-3p in melanoma indicate the potential implication of miR-130b-3p in this malignancy. Herein, we aimed to identify whether and how miR-130b-3p regulated ferroptosis in melanoma cells. Melanoma cells (A375, G-361) were treated with erastin or RSL3 to mimic ferroptosis in vitro. Viability, lipid peroxidation level and ferrous ion content in melanoma cells were then assessed in response to manipulation of miR-130b-3p expression. Luciferase assay was conducted to determine the binding of miR-130b-3p to Dickkopf1 (DKK1). Western blot assay was conducted to determine the expression of molecules related to nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. The results indicated that miR-130b-3p exerted an inhibitory role in erastin or RSL3-induced ferroptosis, evidenced by reductions in lipid peroxidation and ferrous ion content. By suppressing the expression of target gene DKK1, miR-130b-3p activated the Nrf2/HO-1 pathway, whereby repressing ferroptosis. miR-130b-3p blocked the antitumor activity of erastin. Further, in vitro findings were reproduced in an in vivo murine model. Together, these data suggest the potential of miR-130b-3p to inhibit ferroptosis in melanoma cells and the mechanism was related to DKK1-mediated Nrf2/HO-1 pathway.

与铁死亡相关的细胞死亡途径与黑色素瘤的进展有关。新出现的数据报告了黑色素瘤中 microRNA (miR)-130b-3p 的上调，表明 miR-130b-3p 在这种恶性肿瘤中的潜在意义。在此，我们旨在确定 miR-130b-3p 是否以及如何调节黑色素瘤细胞中的铁死亡。用erastin或RSL3处理黑色素瘤细胞（A375、G-361）以模拟体外铁死亡。然后响应于 miR-130b-3p 表达的操作评估黑色素瘤细胞中的活力、脂质过氧化水平和亚铁离子含量。进行荧光素酶测定以确定 miR-130b-3p 与 Dickkopf1 (DKK1) 的结合。进行蛋白质印迹测定以确定与核因子-红细胞2 p45相关因子2（Nrf2）/血红素加氧酶1（HO-1）途径相关的分子的表达。结果表明，miR-130b-3p 在erastin 或RSL3 诱导的铁死亡中发挥抑制作用，这通过脂质过氧化和亚铁离子含量的降低来证明。通过抑制靶基因 DKK1 的表达，miR-130b-3p 激活了 Nrf2/HO-1 通路，从而抑制了铁死亡。miR-130b-3p 阻断了erastin 的抗肿瘤活性。此外，体外研究结果在体内鼠模型中重现。总之，这些数据表明 miR-130b-3p 具有抑制黑色素瘤细胞铁死亡的潜力，其机制与 DKK1 介导的 Nrf2/HO-1 通路有关。从而抑制铁死亡。miR-130b-3p 阻断了erastin 的抗肿瘤活性。此外，体外研究结果在体内鼠模型中重现。总之，这些数据表明 miR-130b-3p 具有抑制黑色素瘤细胞铁死亡的潜力，其机制与 DKK1 介导的 Nrf2/HO-1 通路有关。从而抑制铁死亡。miR-130b-3p 阻断了erastin 的抗肿瘤活性。此外，体外研究结果在体内鼠模型中重现。总之，这些数据表明 miR-130b-3p 具有抑制黑色素瘤细胞铁死亡的潜力，其机制与 DKK1 介导的 Nrf2/HO-1 通路有关。