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转录组分析揭示异甘草素(ISO)对高度侵袭性人膀胱癌 T24 细胞的抗癌作用。

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells.

机构信息

Division of Environmental Medicine, Department of Medicine, NYU Grossman School of Medicine, 341 East 25th Street, New York, NY 10010, USA.

出版信息

Int J Mol Sci. 2024 Feb 1;25(3):1783. doi: 10.3390/ijms25031783.

DOI:10.3390/ijms25031783
PMID:38339062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10855786/
Abstract

Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb , exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.

摘要

膀胱癌是最常见的泌尿系恶性肿瘤,当肿瘤发生肌层浸润时,总体生存率较差。因此,发现和评估针对高级别肌层浸润性膀胱癌(MIBC)的新型替代药物对于降低膀胱癌死亡率具有重要意义。异落叶松脂素(ISO)是一种来自中药的二苯乙烯衍生物,对 MIBC 具有很强的抗癌作用。在这里,我们报告了 ISO 处理人膀胱癌 T24 细胞的全转录组谱分析。共鉴定出 1047 个差异表达基因(DEGs),包括 596 个下调基因和 451 个上调基因。功能注释和通路分析表明,ISO 处理诱导了与细胞运动、迁移、侵袭、代谢、增殖和血管生成相关的大量基因表达变化。此外,ISO 处理激活了参与炎症反应的基因,但抑制了参与缺氧信号转导、糖酵解、肌动蛋白细胞骨架和肿瘤微环境的基因。总之,我们的全转录组分析表明,ISO 处理的 T24 细胞中的代谢发生了转变,肌动蛋白细胞骨架发生了改变,这随后有助于抑制肿瘤生长和进展的肿瘤微环境重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4633/10855786/061f739501ff/ijms-25-01783-g007.jpg
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