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聚苯乙烯微球可通过USP39/IGF2BP3/MAPK4轴抑制前列腺癌细胞的铁死亡。

Polystyrene microspheres could inhibit the ferroptosis of prostate cancer cells via USP39/IGF2BP3/MAPK4 axis.

作者信息

Lu Shengming, Wu Ruipeng, Li Weijian, Fu Zhenyu, Ding Xuefei, Luan Yang, Tianbao Huang, Huang Yuhua

机构信息

Department of Urology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.

Department of Urology, Second People's Hospital of Bengbu City, Bengbu, Anhui, China.

出版信息

J Transl Med. 2025 Aug 11;23(1):891. doi: 10.1186/s12967-025-06868-7.

Abstract

BACKGROUND

Polystyrene (PS) particles, which have been recognized as emerging environmental pollutants, have increasingly been associated with various human diseases. However, their specific role and underlying mechanisms in prostate cancer development have not been fully elucidated.

METHODS

We investigated the characterization properties of PS particles. Subsequently, we examined the impact of PS particles on prostate cancer proliferation using in vitro experiments. Through mRNA sequencing, RIP, and mass spectrometry analysis, we confirmed a close interaction among USP39, IGF2BP3, and MAPK4. The rescue experiment demonstrated that ferroptosis is intricately involved in this process. To further validate our results, we performed mouse xenograft experiments.

RESULTS

In this study, PS particles significantly enhanced the proliferation, migration, and invasion of prostate cancer cells through the regulation of ferroptosis. It was found that USP39 interacts with IGF2BP3, which, in turn, stabilizes MAPK4, a key regulator of ferroptosis.

CONCLUSIONS

These findings illuminate the complex relationship between environmental pollutants such as PS and cancer progression, offering new avenues for research and potential therapeutic interventions in prostate cancer.

摘要

背景

聚苯乙烯(PS)颗粒已被公认为新兴的环境污染物,越来越多地与各种人类疾病相关联。然而,它们在前列腺癌发展中的具体作用和潜在机制尚未完全阐明。

方法

我们研究了PS颗粒的特性。随后,我们通过体外实验检测了PS颗粒对前列腺癌增殖的影响。通过mRNA测序、RIP和质谱分析,我们证实了USP39、IGF2BP3和MAPK4之间存在密切相互作用。挽救实验表明铁死亡复杂地参与了这一过程。为了进一步验证我们的结果,我们进行了小鼠异种移植实验。

结果

在本研究中,PS颗粒通过调节铁死亡显著增强了前列腺癌细胞的增殖、迁移和侵袭。发现USP39与IGF2BP3相互作用,而IGF2BP3又稳定了铁死亡的关键调节因子MAPK4。

结论

这些发现阐明了PS等环境污染物与癌症进展之间的复杂关系,为前列腺癌的研究和潜在治疗干预提供了新的途径。

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