High-throughput sequencing reveals crebanine inhibits colorectal cancer by modulating Tregs immune prognostic target genes

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-15 DOI:10.1515/oncologie-2024-0073

Jiajun Xu, Lingyu Huang, Yu Sha, Chune Mo, Weiwei Gong, Xiayu Tian, Xianliang Hou, Wei Chen, Minglin Ou

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引用次数: 0

Abstract

Crebanine, an alkaloid exhibiting sedative, anti-inflammatory, and anticancer properties, remains unexplored in terms of its anticancer potential against colorectal cancer (CRC). This study aims to bridge this knowledge gap, specifically investigating whether crebanine can suppress CRC and elucidating its underlying molecular mechanism. We employed the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, cell scratch assay, and flow cytometry to observe the effects of crebanine on the growth, migration, and apoptosis of CRC SW480 cells, respectively. High-throughput sequencing was employed to detect differentially expressed genes (DEGs) in SW480 cells treated with crebanine. Enriched pathways of these DEGs were identified through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Genes exhibiting the highest correlation in the enriched pathway were further analyzed using clinical data from The Cancer Genome Atlas Program (TCGA) public database, utilizing R software. Crebanine effectively inhibited the proliferation, migration, and invasion of SW480 cells, with concentrations of ≥15 μg/mL promoting apoptosis. Analysis revealed that the function of DEGs linked to the most enriched pathways was associated with immune infiltration by regulatory T cells (Tregs). When analyzed in conjunction with clinical data, the genes exhibiting the highest correlation in the enrichment pathway were found to be directly associated with clinical prognostic survival. Our study demonstrates that crebanine inhibits colorectal cancer by regulating prognostic target genes related to Tregs. This finding offers a novel approach for pharmacological inhibition and Tregs-targeted therapy in CRC.

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高通量测序揭示克里巴宁通过调节Tregs免疫预后靶基因抑制结直肠癌

克利巴宁是一种具有镇静、抗炎和抗癌特性的生物碱，但其对结肠直肠癌（CRC）的抗癌潜力仍未得到探索。本研究旨在弥补这一知识空白，特别是研究克利巴宁是否能抑制 CRC 并阐明其潜在的分子机制。我们采用 MTT（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴化物）试验、细胞划痕试验和流式细胞术分别观察了克利巴宁对 CRC SW480 细胞生长、迁移和凋亡的影响。利用高通量测序技术检测了经克瑞班宁处理的 SW480 细胞中的差异表达基因（DEGs）。通过基因本体（GO）和京都基因和基因组百科全书（KEGG）分析，确定了这些 DEGs 的丰富通路。利用 R 软件，结合癌症基因组图谱计划（TCGA）公共数据库中的临床数据，进一步分析了富集通路中相关性最高的基因。克瑞巴因可有效抑制SW480细胞的增殖、迁移和侵袭，浓度≥15 μg/mL时可促进细胞凋亡。分析表明，与最丰富通路相关的 DEGs 的功能与调节性 T 细胞（Tregs）的免疫浸润有关。在结合临床数据进行分析时，发现富集通路中相关性最高的基因与临床预后存活率直接相关。我们的研究表明，克瑞巴因通过调节与Tregs相关的预后靶基因来抑制结直肠癌。这一发现为 CRC 的药物抑制和 Tregs 靶向治疗提供了一种新方法。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.