Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2025-01-16 DOI:10.1186/s10020-025-01073-0

Shengkai Jin, Yuhua Zhou, Jing Lv, Yichen Lu, Yuwei Zhang, Menglu Li, Ninghan Feng

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引用次数: 0

Abstract

Background: A close relationship exists between castration-resistant prostate cancer (CRPC) and histidine metabolism by gut microbes. However, the effects of the histidine metabolite imidazole propionate (IMP) on prostate cancer (PCa) and its underlying mechanisms are not well understood.

Methods: We first assessed the effects of IMP on cell proliferation and migration at the cellular level. Subsequently, we investigated the mechanism of action of IMP using transcriptome sequencing, qPCR, and Western blot analysis. Finally, we validated our findings in vivo using a mouse model.

Results: Histidine had no effect on PCa cell proliferation; however, IMP significantly inhibited the proliferation and migration of PC3 and DU145 cells. Mechanistic studies indicate that IMP exerts its effects by upregulating PDZK1 expression, which subsequently inhibits the phosphorylation of the PI3K-AKT pathway.

Conclusions: In conclusion, IMP significantly inhibits the progression of PCa, offering new insights into potential treatments for CRPC.

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微生物产生的咪唑丙酸通过PDZK1损害前列腺癌的进展。

背景：去势抵抗性前列腺癌（CRPC）与肠道微生物组氨酸代谢密切相关。然而，组氨酸代谢物丙酸咪唑（IMP）对前列腺癌（PCa）的作用及其潜在机制尚不清楚。方法：我们首先在细胞水平上评估IMP对细胞增殖和迁移的影响。随后，我们利用转录组测序、qPCR和Western blot分析研究了IMP的作用机制。最后，我们用小鼠模型在体内验证了我们的发现。结果：组氨酸对PCa细胞增殖无影响；然而，IMP明显抑制PC3和DU145细胞的增殖和迁移。机制研究表明，IMP通过上调PDZK1表达发挥作用，进而抑制PI3K-AKT通路的磷酸化。结论：综上所述，IMP显著抑制了PCa的进展，为CRPC的潜在治疗提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.