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丹皮酚通过 miR-3194-5p/连环蛋白β相互作用蛋白 1 轴抑制结直肠癌细胞干性。

Paeoniflorin inhibits colorectal cancer cell stemness through the miR-3194-5p/catenin beta-interacting protein 1 axis.

机构信息

The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.

Tumor Hematology Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.

出版信息

Kaohsiung J Med Sci. 2023 Oct;39(10):1011-1021. doi: 10.1002/kjm2.12736. Epub 2023 Aug 2.

Abstract

Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/β-catenin axis to repress CRC cell stemness.

摘要

芍药苷(PF)是一种具有显著抗肿瘤作用的天然植物成分。在此,我们研究了 PF 在结直肠癌(CRC)细胞干性中的生物学效应和机制。信使 RNA(mRNA)和蛋白质表达通过定量实时聚合酶链反应和 Western blot 进行评估。CRC 细胞的活力、增殖、迁移和侵袭分别通过细胞计数试剂盒-8、克隆形成和 Transwell 迁移和侵袭实验进行评估。球体形成能力通过球体形成实验确定。双荧光素酶报告基因实验用于分析 miR-3194-5p 和连环蛋白 β 相互作用蛋白 1(CTNNBIP1)之间的相互作用。PF 抑制 CRC 细胞活力、迁移、侵袭、上皮-间充质转化和干性。miR-3194-5p 在 CRC 组织和细胞中上调。miR-3194-5p 敲低抑制 CRC 细胞干性,而 miR-3194-5p 过表达则产生相反的效果。此外,PF 对 CRC 细胞干性的抑制作用被 miR-3194-5p 过表达所消除。CTNNBIP1 是 miR-3194-5p 的靶基因,其敲低消除了 PF 对 CRC 细胞干性和 Wnt/β-catenin 信号激活的抑制作用。PF 通过调节 miR-3194-5p/CTNNBIP1/Wnt/β-catenin 轴来抑制 CRC 细胞干性。

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