The BMI1-Angiopoietin-2 axis as an independent prognostic factor in colorectal cancer

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-05-29 DOI:10.1016/j.yexcr.2025.114622

Yin-Chou Hsu , Chi-Wen Luo , Shu-Jyuan Chang , Chiao-Ying Lai , Yu-Tzu Yang , Yi-Zi Chen , Mei-Hsiang Hsu , Cheuk-Kwan Sun , Mei-Ren Pan

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引用次数: 0

Abstract

Background

The polycomb group protein B-lymphoma Moloney murine leukemia virus Insertion region-1 (BMI1), a transcriptional repressor, has been implicated in colorectal cancer (CRC) progression. This study investigated the role of BMI1 in the regulation of angiogenesis and its association with angiopoietin 2 (ANGPT2) in CRC.

Methods

The highly metastatic CRC cell line SW620, known for its high BMI1 expression, was used to examine the effects of BMI1 knockdown and pharmacological inhibition using PTC209. Angiogenesis was assessed by tube formation and transendothelial migration assays. Quantitative real-time polymerase chain reaction (RT-qPCR) arrays were conducted to identify angiogenesis-related genes, and bioinformatics analysis using the TIMER database (version 2.0) was used to validate the correlation between BMI1 and angiogenic factors. Western blotting and immunohistochemistry confirmed protein-level interactions in cell and tissue samples. Clinicopathological associations were analyzed in 44 patients with advanced CRC, using survival analysis and multivariate regression models.

Results

BMI1 knockdown significantly reduced tube formation and endothelial cell adhesion in SW620 cells. RT-qPCR and database analyses revealed a strong positive correlation between BMI1 and ANGPT2 expression (r = 0.366, p < 0.05). Protein-level analysis confirmed that BMI1 is essential for ANGPT2 expression, which was further validated in CRC clinical specimens and showed a significant correlation (p = 0.039). Survival analysis indicated that high BMI1 and ANGPT2 expression levels were significantly associated with poor overall survival and progression-free survival (p < 0.05).

Conclusion

BMI1 promotes angiogenesis in CRC by upregulating ANGPT2 expression. High BMI1 and ANGPT2 levels served as independent prognostic factors for tumor progression, highlighting their potential as therapeutic targets for CRC management.

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bmi1 -血管生成素-2轴作为结直肠癌的独立预后因素。

背景：polycomb group protein b -淋巴瘤Moloney小鼠白血病病毒插入区1 （BMI1）是一种转录抑制因子，与结直肠癌（CRC）的进展有关。本研究探讨了BMI1在CRC血管生成调控中的作用及其与血管生成素2 （ANGPT2）的关联。方法：以BMI1高表达的CRC高转移细胞系SW620为研究对象，采用PTC-209检测BMI1敲除和药理抑制的作用。血管生成通过管形成和跨内皮迁移试验进行评估。采用实时定量聚合酶链反应（RT-qPCR）阵列技术鉴定血管生成相关基因，利用TIMER数据库（2.0版）进行生物信息学分析，验证BMI1与血管生成因子的相关性。Western blotting和免疫组织化学证实了细胞和组织样品中蛋白水平的相互作用。采用生存分析和多变量回归模型分析44例晚期结直肠癌患者的临床病理相关性。结果：BMI1基因敲除显著减少SW620细胞的小管形成和内皮细胞粘附。RT-qPCR和数据库分析显示，BMI1与ANGPT2表达呈正相关（r = 0.366, p < 0.05）。蛋白水平分析证实BMI1对ANGPT2的表达至关重要，在结直肠癌临床标本中进一步证实了这一点，并显示出显著的相关性（p = 0.039）。生存分析显示，BMI1和ANGPT2高表达水平与总生存期和无进展生存期差显著相关（p < 0.05）。结论：BMI1通过上调ANGPT2表达促进结直肠癌血管生成。高BMI1和ANGPT2水平是肿瘤进展的独立预后因素，突出了它们作为结直肠癌治疗靶点的潜力。

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

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.