MST1R-targeted therapy in the battle against gallbladder cancer.

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell and Bioscience Pub Date : 2024-08-29 DOI:10.1186/s13578-024-01290-w

Wei Wang, Chao Huang, Li Zhang, Liqin Yu, Yangming Liu, Puxiongzhi Wang, Rongmu Xia

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引用次数: 0

Abstract

Background: Gallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC.

Results: Bioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC.

Conclusion: Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.

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抗击胆囊癌的 MST1R 靶向疗法。

背景：胆囊癌（GBC）的特点是死亡率高。我们的研究旨在寻找治疗 GBC 的候选药物：生物信息学分析发现 MST1R 在 GBC 中显著上调。体外实验表明，MST1R抑制剂MGCD-265在较低浓度下可有效抑制GBC细胞增殖。此外，它还能以剂量依赖的方式诱导 GBC 细胞周期停滞和凋亡。小鼠模型显示，MGCD-265 能显著降低 GBC-SD 细胞的增殖能力。转录组学测序揭示了转录组的显著改变，其中200个转录本上调，883个下调。KEGG和GO分析强调了细胞粘附等过程和蛋白质消化吸收等通路的富集。下游基因分析发现 JMJD6 在 MGCD-265 处理后上调。体内实验证实，将MGCD-265与JMJD6抑制剂SKLB325结合使用可增强对GBC的抗癌效果：总之，靶向 MST1R 及其下游基因，尤其是将 MGCD-265 与 SKLB325 结合使用，有望成为 GBC 的一种治疗策略。

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

Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

10.70

自引率

0.00%

发文量

187

审稿时长

>12 weeks

期刊介绍： Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.