人参皂苷Rk1通过影响mRNA的m6A修饰抑制肝细胞癌的上皮-间质转化和转移
Ginsenoside Rk1 inhibits EMT and the metastasis of hepatocellular carcinoma by affecting the m6A modification of mRNA.
摘要(中文译文)
N6-甲基腺苷（m6A）是一种关键的信使RNA（mRNA）修饰，在肿瘤发展和转移中发挥重要作用。人参皂苷Rk1具有显著的抗癌活性，但其对m6A修饰的影响尚未阐明。本研究旨在探讨人参皂苷Rk1在调控m6A修饰中的作用及其对肝细胞癌（HCC）转移的影响。通过构建体外和体内肺转移模型，研究人参皂苷Rk1对HCC肺转移的影响。采用RNA测序、m6A测序、siRNA细胞转染、蛋白质印迹和实时定量PCR（qRT-PCR）研究人参皂苷Rk1对m6A修饰的影响及其通过调节m6A修饰抑制肺转移的作用机制。人参皂苷Rk1在体内和体外均表现出对HCC转移的剂量依赖性抑制作用。在机制上，它抑制了m6A去甲基化酶脂肪量和肥胖相关蛋白（FTO）的表达，从而增强了HCC细胞中的m6A修饰。具体而言，人参皂苷Rk1显著增加了增殖阻滞蛋白1（BOP1）mRNA的m6A修饰，导致mRNA半衰期延长。此外，人参皂苷Rk1介导的BOP1表达敲低抑制了上皮-间质转化（EMT）通路相关蛋白（如波形蛋白、基质金属蛋白酶-2（MMP2）和基质金属蛋白酶-9（MMP9）），从而减弱了HCC细胞的转移潜能。这些发现凸显了人参皂苷Rk1通过调节FTO-m6A-BOP1轴和抑制EMT通路的双重作用来减轻HCC侵袭性的治疗潜力。人参皂苷Rk1通过增强FTO介导的BOP1 mRNA的m6A修饰来抑制HCC的迁移和侵袭。人参皂苷Rk1有潜力作为m6A甲基化调节抑制剂，为靶向m6A修饰治疗HCC转移提供了新途径。
Abstract
N6-methyladenosine (m6A) is a crucial messenger RNA (mRNA) modification that plays a significant role in tumor development and metastasis. Ginsenoside Rk1 possesses notable anticancer activity; however, its effects on m6A modification have not yet been elucidated. In this study, the aim is to investigate the role of ginsenoside Rk1 in the regulation of m6A modification and its effect on hepatocellular carcinoma (HCC) metastasis. The construction of in vitro and in vivo lung metastasis models was used to investigate the effect of ginsenoside Rk1 on lung metastasis of HCC. RNA sequencing, m6A sequencing, siRNA cell transfection, western blotting and quantitative real-time PCR (qRT-PCR) were performed to investigate the effect of ginsenoside Rk1 on m6A modification and its mechanism of action in inhibiting lung metastasis through modulation of m6A modification. Ginsenoside Rk1 demonstrated dose-dependent inhibition of HCC metastasis both in vivo and in vitro. Mechanistically, it suppressed the expression of Fat mass and obesity-associated protein (FTO), an m6A demethylase, thereby enhancing m6A modification in HCC cells. Specifically, ginsenoside Rk1 significantly increased the m6A modification of Block of proliferation 1 (BOP1) mRNA, leading to prolonged mRNA half-life. Furthermore, ginsenoside Rk1-mediated knockdown of BOP1 expression inhibited Epithelial-mesenchymal transition (EMT) pathway-related proteins (e.g., Vimentin, matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9)), thus attenuating the metastatic potential of HCC cells. These findings highlighted the therapeutic potential of ginsenoside Rk1 in mitigating HCC aggressiveness through its dual role in modulating the FTO-m6A-BOP1 axis and inhibiting the EMT pathway. Ginsenoside Rk1 inhibits the migration and invasion of HCC by enhancing FTO-mediated m6A modification of BOP1 mRNA. Ginsenoside Rk1 has the potential to act as an m6A methylation regulator inhibitor, offering a novel approach for targeting m6A modification in the treatment of HCC metastasis.
如何引用
AMA
Huanyan Wu, Yuan Liu, Chenhui Zhu, Zhiguang Duan, Linlin Qu, Rongzhan Fu. Ginsenoside Rk1 inhibits EMT and the metastasis of hepatocellular carcinoma by affecting the m6A modification of mRNA.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158532.
APA
Huanyan Wu, Yuan Liu, Chenhui Zhu, Zhiguang Duan, Linlin Qu, Rongzhan Fu (2026). Ginsenoside Rk1 inhibits EMT and the metastasis of hepatocellular carcinoma by affecting the m6A modification of mRNA.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158532
GB/T 7714
Huanyan Wu, Yuan Liu, Chenhui Zhu, Zhiguang Duan, Linlin Qu, Rongzhan Fu. Ginsenoside Rk1 inhibits EMT and the metastasis of hepatocellular carcinoma by affecting the m6A modification of mRNA.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158532.
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