白头翁煎剂通过 miR-495-3p/BUB1/STAT3 轴抑制食管癌细胞的生长

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY World Journal of Gastrointestinal Oncology Pub Date : 2024-07-15 DOI:10.4251/wjgo.v16.i7.3193
Hui Yang, Xiao-Wei Chen, Xue-Jie Song, Hai-Yang Du, Fu-Chun Si
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The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively.\n RESULTS\n DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. 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引用次数: 0

摘要

背景食管癌(EC)是全球人口中发病率最高的癌症之一。白头翁煎是最重要的中药配方之一,具有治疗癌症的潜力。目的 研究白头翁煎剂对癌细胞的作用和机制。方法 通过 cDNA 微阵列技术和生物信息学方法筛选心肌组织和正常组织中的差异表达基因(DEGs)。根据 TargetScan 数据库预测 microRNA 的靶基因,并通过双荧光素酶基因报告实验进行验证。我们使用白头翁煎剂干预EC细胞,并用MTT法检测EC9706和KYSE150细胞的活性。流式细胞术检测细胞周期和细胞凋亡。通过 qRT-PCR 检测 BUB1 mRNA 和 miR-495-3p 的表达。通过 Western 印迹分析测定了 BUB1、STAT3、p-STAT3、CCNB1、CDK1、Bax、Caspase3 和 Caspase9 的蛋白水平。伤口愈合试验和 Transwell 侵袭试验分别测定了细胞的迁移和侵袭能力。结果 发现的 DEGs 参与了生物过程、信号通路和网络构建,主要与有丝分裂有关。BUB1是关键的枢纽基因,也是miR-495-3p的靶基因。白头翁煎剂能上调 miR-495-3p 并抑制 BUB1 的表达。体外实验表明,白头翁水煎剂能显著抑制 EC 细胞的迁移和侵袭,诱导细胞凋亡和 G2/M 期停滞。经白头翁煎剂处理后,EC细胞中Bax、Caspase 3和Caspase 9的表达明显增加,而BUB1、CCNB1和CDK1的表达则明显减少。此外,STAT3 信号通路可能在这一过程中发挥了重要作用。结论 白头翁煎剂对心肌细胞的生长有明显的抑制作用。BUB1 是治疗心血管疾病的潜在靶点。进一步分析表明,白头翁煎剂可通过上调针对 BUB1 介导的 STAT3 信号通路的 miR-495-3p 来抑制心肌细胞的生长。
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Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis
BACKGROUND Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. AIM To investigate the role and mechanism of Baitouweng decoction on EC cells. METHODS Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively. RESULTS DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process. CONCLUSION Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.
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来源期刊
World Journal of Gastrointestinal Oncology
World Journal of Gastrointestinal Oncology Medicine-Gastroenterology
CiteScore
4.20
自引率
3.30%
发文量
1082
期刊介绍: The World Journal of Gastrointestinal Oncology (WJGO) is a leading academic journal devoted to reporting the latest, cutting-edge research progress and findings of basic research and clinical practice in the field of gastrointestinal oncology.
期刊最新文献
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