Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma,Journal of Proteome Research

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Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-05-24 , DOI: 10.1021/acs.jproteome.8b00181
Jing Yang _{1,

2} , Qi Xie _{1,

2,

3} , Hui Zhou ₁ , Lei Chang ₂ , Wei Wei ₂ , Yin Wang _{1,

2} , Hong Li ₄ , Zixin Deng ₁ , Yuling Xiao ₁ , Junzhu Wu ₃ , Ping Xu _{1,

2,

5} , Xuechuan Hong _{1,

6}

Affiliation

Targeted therapy of hepatocellular carcinoma (HCC) is essential for improved therapies. Therefore, identification of key targets specifically to HCC is an urgent requirement. Herein, an iTRAQ quantitative proteomic approach was employed to identify differentially expressed proteins in HCC tumor tissues. Of the upregulated tumor-related proteins, minichromosome maintenance 2 (MCM2), a DNA replication licensing factor, was one of the most significantly altered proteins, and its overexpression was confirmed using tissue microarray. Clinicopathological analysis of multiple cohorts of HCC patients indicated that overexpression of MCM2 was validated in 89.8% tumor tissues and strongly correlated with clinical stage. Furthermore, siRNA-mediated repression of MCM2 expression resulted in significant suppression of the HepG2 cell cycle and proliferation through the cyclin D-dependent kinases (CDKs) 2/7 pathway. Finally, the first small molecule-based MCM2-targeted NIR-II probe CH1055-MCM2 was concisely generated and subsequently evaluated in mice bearing HepG2 xenografts. The excellent imaging properties such as good tumor uptake and high tumor contrast and specificity were achieved in the small animal models. This analytical strategy can determine novel accessible targets of HCC useful for imaging and therapy.

中文翻译：

肝细胞癌MCM2蛋白的蛋白质组学分析和NIR-II成像

肝细胞癌（HCC）的靶向治疗对于改善治疗至关重要。因此，迫切需要确定专门针对HCC的关键指标。本文中，采用iTRAQ定量蛋白质组学方法来鉴定HCC肿瘤组织中差异表达的蛋白质。在上调的肿瘤相关蛋白中，微染色体维持蛋白2（MCM2）是DNA复制许可因子，是变化最严重的蛋白之一，其超表达已通过组织微阵列得到证实。对多组HCC患者的临床病理分析表明，MCM2的过表达在89.8％的肿瘤组织中得到证实，并且与临床分期密切相关。此外，siRNA介导的MCM2表达抑制通过细胞周期蛋白D依赖性激酶（CDKs）2/7途径显着抑制HepG2细胞周期和增殖。最后，第一个基于小分子的MCM2靶向NIR-II探针简明地生成CH1055-MCM2，然后在带有HepG2异种移植物的小鼠中进行评估。在小动物模型中获得了出色的成像特性，例如良好的肿瘤吸收以及高的肿瘤对比度和特异性。这种分析策略可以确定对影像学和治疗有用的新型HCC靶标。

更新日期：2018-05-25

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