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膀胱癌细胞系的定量蛋白质组学研究发现 UAP1 是一个有潜力的治疗靶点。

Quantitative Proteomics of Urinary Bladder Cancer Cell Lines Identify UAP1 as a Potential Therapeutic Target.

机构信息

Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.

Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India.

出版信息

Genes (Basel). 2020 Jul 8;11(7):763. doi: 10.3390/genes11070763.

Abstract

Bladder carcinoma (BC) incidence and mortality rates are increasing worldwide. The development of novel therapeutic strategies is required to improve clinical management of this cancer. Aberrant protein expression may lead to cancer initiation and progression. Therefore, the identification of these potential protein targets and limiting their expression levels would provide alternative treatment options. In this study, we utilized a liquid-chromatography tandem mass spectrometry-based global proteomics approach to identify differentially expressed proteins in bladder cancer cell lines. A total of 3913 proteins were identified in this study, of which 479 proteins were overexpressed and 141 proteins were downregulated in 4 out of 6 BC cell lines when compared with normal human urothelial cell line (TERT-NHUC). We evaluated the role of UDP-N-acetylhexosamine pyrophosphorylase (UAP1) in bladder cancer pathogenesis. The silencing of UAP1 led to reduction in proliferation, invasion, colony formation and migration capability of bladder cancer cell lines. Thus, our study reveals UAP1 as a promising therapeutic target for bladder cancer.

摘要

膀胱癌(BC)的发病率和死亡率在全球范围内呈上升趋势。需要开发新的治疗策略来改善这种癌症的临床管理。异常的蛋白质表达可能导致癌症的发生和发展。因此,鉴定这些潜在的蛋白质靶标并限制其表达水平将提供替代治疗选择。在这项研究中,我们利用基于液相色谱串联质谱的全局蛋白质组学方法来鉴定膀胱癌细胞系中差异表达的蛋白质。在这项研究中鉴定了 3913 种蛋白质,其中 479 种蛋白质在 6 种膀胱癌细胞系中的 4 种与正常人类尿路上皮细胞系(TERT-NHUC)相比过度表达,而 141 种蛋白质下调。我们评估了 UDP-N-乙酰氨基葡萄糖焦磷酸化酶(UAP1)在膀胱癌发病机制中的作用。UAP1 的沉默导致膀胱癌细胞系增殖、侵袭、集落形成和迁移能力降低。因此,我们的研究揭示了 UAP1 作为膀胱癌有前途的治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2655/7397020/2bd1c976fd1d/genes-11-00763-g001.jpg

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