Characterization of HMGB1/2 Interactome in Prostate Cancer by Yeast Two Hybrid Approach: Potential Pathobiological Implications
Characterization of HMGB1/2 Interactome in Prostate Cancer by Yeast Two Hybrid Approach: Potential Pathobiological Implications
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DOI：
10.3390/cancers11111729
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发表时间：
2019-11-01
期刊：
影响因子：
5.2
通讯作者：
Cerdan, Maria-Esperanza
中科院分区：
文献类型：
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作者：
Barreiro-Alonso, Aida;Camara-Quilez, Maria;Cerdan, Maria-Esperanza
高迁移率族蛋白B（HMGB）蛋白在癌症的发展中是关键的。虽然已经报道了前列腺癌（PCa）细胞的蛋白质组学，但HMGB蛋白及其相互作用组在PCa中的参与是一个相当感兴趣的未探索的领域。我们在此描述了第一个HMGB 1/HMGB 2相互作用组方法治疗PCa的结果。使用HMGB 1和HMGB 2诱饵，通过酵母双杂交方法（Y2 H）筛选由PCa细胞系PC-3和患者的PCa原发性肿瘤构建的文库。这种PCa HMGB相互作用组的功能意义已经通过公共数据库上可用的表达和预后数据进行了验证。影响这些新描述的HMGB相互作用组成分的拷贝数改变（CNA）在最具侵袭性的PCa形式中更常见：神经内分泌起源或去势抵抗的PCa。一致地，在这些基因中显示CNA的腺癌PCa样品也与更差的预后相关。这些发现为它们作为区分高风险和低风险患者的生物标志物的潜在用途开辟了道路。在HMGB 1和HMGB 2沉默后，通过qPCR分析了这些相互作用组组分的选定组的基因表达。这些数据表明，HMGB 1和HMGB 2控制着它们的几个相互作用组伙伴的表达，这可能有助于这些蛋白在PCa中的协调作用。
High mobility group box B (HMGB) proteins are pivotal in the development of cancer. Although the proteomics of prostate cancer (PCa) cells has been reported, the involvement of HMGB proteins and their interactome in PCa is an unexplored field of considerable interest. We describe herein the results of the first HMGB1/HMGB2 interactome approach to PCa. Libraries constructed from the PCa cell line, PC-3, and from patients' PCa primary tumor have been screened by the yeast 2-hybrid approach (Y2H) using HMGB1 and HMGB2 baits. Functional significance of this PCa HMGB interactome has been validated through expression and prognosis data available on public databases. Copy number alterations (CNA) affecting these newly described HMGB interactome components are more frequent in the most aggressive forms of PCa: those of neuroendocrine origin or castration-resistant PCa. Concordantly, adenocarcinoma PCa samples showing CNA in these genes are also associated with the worse prognosis. These findings open the way to their potential use as discriminatory biomarkers between high and low risk patients. Gene expression of a selected set of these interactome components has been analyzed by qPCR after HMGB1 and HMGB2 silencing. The data show that HMGB1 and HMGB2 control the expression of several of their interactome partners, which might contribute to the orchestrated action of these proteins in PCa