Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma.
Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma.
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DOI：
10.1021/acs.jproteome.8b00181
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发表时间：
2018-05
影响因子：
4.4
通讯作者：
Jing Yang;Qi Xie;Hui Zhou;Lei Chang;Wei Wei-Wei;Yin Wang;Hong Li;Z. Deng;Yuling Xiao;Junzhu Wu;P. Xu;Xuechuan Hong
中科院分区：
文献类型：
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作者：
Jing Yang;Qi Xie;Hui Zhou;Lei Chang;Wei Wei-Wei;Yin Wang;Hong Li;Z. Deng;Yuling Xiao;Junzhu Wu;P. Xu;Xuechuan Hong
肝细胞癌的靶向治疗是提高治疗水平的关键。因此，识别针对肝细胞癌的关键靶点是当务之急。在此，我们采用iTRAQ定量蛋白质组学方法来鉴定肝细胞癌组织中差异表达的蛋白质。在上调的肿瘤相关蛋白中，微小染色体维持2(MCM2)是一种DNA复制许可因子，是变化最显著的蛋白之一，组织芯片证实其过表达。临床病理分析表明，MCM2在89.8%的肿瘤组织中过表达，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依赖的激酶(CDKs)2/7途径显著抑制了HepG2细胞的周期和增殖。最后，第一个基于小分子的MCM2靶向NIR-II探针CH1055-MCM2被简明地制造出来，并随后在携带HepG2异种移植瘤的小鼠身上进行了评估。在小动物模型中获得了良好的肿瘤摄取、较高的肿瘤对比度和特异性等良好的成像特性。这一分析策略可以确定新的可接近的肝癌靶点，对成像和治疗有用。
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.