MicroRNA-150-5p 通过靶向 NEDD4 结合蛋白 2-like 1 基因介导的膀胱癌细胞增殖、G1/S 转变和迁移抑制作用

IF 1.4 4区 医学 Q4 PHYSIOLOGY Chinese Journal of Physiology Pub Date : 2024-05-06 DOI:10.4103/ejpi.ejpi-d-24-00009
Pinlang Rao, Jianmin Li, Junhui Xiong, Siyao Shen, Jingwen Zeng, Hong Zhao
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引用次数: 0

摘要

微RNA-150-5p(miR-150-5p)与多种癌症类型的进展有关,但其在膀胱癌(BC)中的具体功能作用和调控机制在很大程度上仍未得到探索。我们的研究利用实时定量聚合酶链反应和 Western 印迹分析发现,与对照组相比,miR-150-5p 在膀胱癌组织中明显下调,而 NEDD4 结合蛋白 2-like 1 基因(N4BP2L1)则明显上调。经Chi-square检验,miR-150-5p表达量减少与肿瘤晚期和淋巴结转移有关,而N4BP2L1水平升高与肿瘤体积增大有关。在功能上,miR-150-5p 对 BC 细胞的增殖、迁移、诱导 G0/G1 期停滞和凋亡有显著的抑制作用。我们利用荧光素酶报告实验证实了 N4BP2L1 是 miR-150-5p 在 BC 细胞中的直接靶点。重要的是,N4BP2L1 的敲除模拟了 miR-150-5p 对 BC 细胞增殖、迁移和侵袭的抑制作用,而过表达则抵消了这种抑制作用。此外,N4BP2L1 的过表达逆转了 miR-150-5p 诱导的 BC 细胞中 CDK4、细胞周期蛋白 D1、Bcl-2、PCNA、Ki-67、N-钙粘蛋白、Bad 和 E-钙粘蛋白水平的变化。基于这些结果,我们可以推断,miR-150-5p/N4BP2L1 轴可能是治疗 BC 的一个有希望的候选靶点。
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MicroRNA-150-5p-mediated Inhibition of Cell Proliferation, G1/S Transition, and Migration in Bladder Cancer through Targeting NEDD4-binding Protein 2-like 1 Gene
MicroRNA-150-5p (miR-150-5p) has been implicated in the progression of several cancer types, yet its specific functional role and regulatory mechanisms in bladder cancer (BC) remain largely unexplored. Our study revealed significant downregulation of miR-150-5p and upregulation of NEDD4-binding protein 2-like 1 gene (N4BP2L1) in BC tissues compared to controls using quantitative real-time polymerase chain reaction and western blot analysis, respectively. Reduced miR-150-5p expression correlated with advanced tumor stage and lymph node metastasis, while increased N4BP2L1 levels were associated with larger tumor size by the Chi-square test. Functionally, miR-150-5p exerted significant inhibitory effects on BC cell proliferation, migration, inducing G0/G1 phase arrest, and apoptosis. We confirmed N4BP2L1 as a direct target of miR-150-5p in BC cells using luciferase reporter assay. Crucially, N4BP2L1 knockdown mimicked, while overexpression counteracted the inhibitory impacts of miR-150-5p on BC cell proliferation, migration, and invasion. In addition, N4BP2L1 overexpression reversed miR-150-5p-induced alterations in CDK4, Cyclin D1, Bcl-2, PCNA, Ki-67, N-cadherin, Bad, and E-cadherin levels in BC cells. Based on these results, it can be inferred that the miR-150-5p/N4BP2L1 axis might constitute a promising candidate for therapeutic targeting in the treatment of BC.
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来源期刊
CiteScore
2.30
自引率
5.60%
发文量
36
审稿时长
6-12 weeks
期刊介绍: Chinese Journal of Physiology is a multidisciplinary open access journal. Chinese Journal of Physiology (CJP) publishes high quality original research papers in physiology and pathophysiology by authors all over the world. CJP welcomes submitted research papers in all aspects of physiology science in the molecular, cellular, tissue and systemic levels. Multidisciplinary sciences with a focus to understand the role of physiology in health and disease are also encouraged. Chinese Journal of Physiology accepts fourfold article types: Original Article, Review Article (Mini-Review included), Short Communication, and Editorial. There is no cost for readers to access the full-text contents of publications.
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