摘要
目的:血管生成是肿瘤生长和转移的关键介质,CDC25B在包括三阴性乳腺癌(Triple-Negative Breast Cancer,TNBC)等恶性肿瘤作为肿瘤癌基因,但其对血管生成的生物学作用知之甚少,本研究旨在探讨CDC25B在TNBC血管生成中的确切功能和作用机制。方法:生信数据库分析CDC25B及其上游调控分子miR-141-3p在TNBC肿瘤组织中的表达,采用qRT-PCR分析CDC25B和miR-141-3p在TNBC细胞系中的表达。利用CCK-8和血管形成实验分析HUVEC细胞的增殖和血管形成能力,并通过Western blot检测VEGFA、VEGFR-2和VEGFR-3蛋白的表达。双荧光素酶报告实验被用于探索CDC25B和miR-141-3p之间的特异性相互作用。结果:本研究发现CDC25B在TNBC中表达上调,其高表达可以激活VEGF信号通路,沉默CDC25B后显著抑制了HUVEC细胞的增殖和血管生成,并降低了VEGFA、VEGFR-2和VEGFR-3蛋白的表达。此外,miR-141-3p在TNBC中表达下调,可以靶向抑制CDC25B的表达。过表达CDC25B可以逆转miR-141-3p过表达对HUVEC细胞增殖和血管生成的抑制作用。结论:miR-141-3p靶向CDC25B抑制VEGF通路抑制TNBC血管生成,为miR-141-3p/CDC25B/VEGF通路可能作为TNBC抗血管生成治疗的新选择提供理论依据。
Objective:To investigate the exact function and mechanism of CDC25B in TNBC angiogenesis.Methods:Bioinformatics database was used to analyze the expressions of CDC25B and its upstream regulatory molecule miR-141-3p in TNBC tumor tissues,and qRT-PCR was used to analyze the expressions of CDC25B and miR-141-3p in TNBC cell lines.The proliferation and angiogenesis capacity of HUVEC cells were analyzed by CCK-8 and angiogenesis assay,and the expressions of VEGFA,VEGFR-2 and VEGFR-3 proteins were detected by Western blot.Dual luciferase reporter assay was used to explore the specific interaction between CDC25B and miR-141-3p.Results:It was found that CDC25B was up-regulated in TNBC,and its high expression could activate the VEGF signaling pathway,and the silencing of CDC25B significantly inhibited the proliferation and angiogenesis of HUVEC cells,and decreased the expression of VEGFA,VEGFR-2 and VEGFR-3 proteins.In addition,the expression of miR-141-3p was down-regulated in TNBC,which could target the inhibition of CDC25B expression.Overexpression of CDC25B reversed the inhibitory effect of miR-141-3p overexpression on proliferation and angiogenesis of HUVEC cells.Conclusion:miR-141-3p targets CDC25B to inhibit VEGF pathway and inhibit TNBC angiogenesis,and we provide theoretical basis for the possibility of miR-141-3p/CDC25B/VEGF pathway as a new choice for TNBC anti-angiogenesis therapy.
作者
陈燕枝
CHEN Yanzhi(Jiangxi Medical College,Jiangxi Shangrao 333400,China)
出处
《河北医学》
CAS
2023年第9期1421-1426,共6页
Hebei Medicine
基金
江西省教育厅科学技术研究项目,(编号:181174)。
