Curzerene通过长链非编码RNA AFAP1-AS1靶向调控YAP，抑制胃癌前病变细胞的上皮-间质转化

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-21 DOI:10.1016/j.phymed.2025.156879

XiaoMing Zhou , ChenXi Zhang , Wen Shen , RuiFei Zhuang , ShenLin Liu , JinDi Liu

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引用次数: 0

摘要

莪术烯是莪术中的一种生物活性化合物，具有抗癌作用，但其在胃癌前病变中的作用尚不清楚。本研究探讨Curzerene通过调节长链非编码RNA (LncRNA) AFAP1-AS1和Hippo/YAP信号通路抑制胃癌前病变进展的潜力。方法用MNNG处理GES-1细胞，建立胃癌前细胞模型（MC细胞）。采用CCK-8、划痕法、RT-PCR和Western blot评估Curzerene对细胞增殖、迁移和EMT的影响。在体内，采用MNU诱导胃癌前小鼠模型，通过组织学和分子分析评价莪术烯（14 mg/kg和28 mg/kg）的治疗效果。结果curzerene可显著抑制MC细胞的增殖、迁移和EMT，下调LncRNA AFAP1-AS1和YAP，上调E-cadherin，下调N-cadherin。在体内，Curzerene减轻了胃粘膜损伤，降低了癌症标志物（P53和CD133），改善了组织病理学。转录组学分析确定Hippo/YAP通路是Curzerene作用的关键中介。YAP的激活逆转了Curzerene对EMT的抑制作用，证实了这一途径的参与。结论curzerene通过靶向YAP信号及以下LncRNA AFAP1-AS1抑制EMT，有效抑制胃癌前病变进展。这些发现表明Curzerene作为一种早期干预和预防胃癌的治疗药物具有新的潜力。

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Curzerene suppresses epithelial-mesenchymal transition in gastric precancerous lesion cells through targeted regulation of YAP via the long non-coding RNA AFAP1-AS1

Background

Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway.

Methods

In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis.

Results

Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway.

Conclusion

Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.