Proteomic Analysis of MYB-Regulated Secretome Identifies Functional Pathways and Biomarkers: Potential Pathobiological and Clinical Implications.,Journal of Proteome Research

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Proteomic Analysis of MYB-Regulated Secretome Identifies Functional Pathways and Biomarkers: Potential Pathobiological and Clinical Implications.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-01-27 , DOI: 10.1021/acs.jproteome.9b00641
Haseeb Zubair _{1,

2} , Girijesh Kumar Patel ₂ , Mohammad Aslam Khan _{1,

2} , Shafquat Azim ₂ , Asif Zubair ₃ , Seema Singh _{1,

2,

4} , Sanjeev Kumar Srivastava _{1,

2} , Ajay Pratap Singh _{1,

2,

4}

Affiliation

Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks, and altered biological pathways. Our data demonstrated significant modulation (p < 0.05) of 337 secreted proteins in MYB-silenced MiaPaCa cells, whereas 282 proteins were differentially present in MYB-overexpressing BxPC3 cells, compared to their respective control cells. Alteration of several phenotypes such as cellular movement, cell death and survival, inflammatory response, protein synthesis, etc. was associated with MYB-induced differentially expressed proteins (DEPs) in secretomes. DEPs from MYB-silenced MiaPaCa PC cells were suggestive of the downregulation of genes primarily associated with glucose metabolism, PI3K/AKT signaling, and oxidative stress response, among others. DEPs from MYB-overexpressing BxPC3 cells suggested the enhanced release of proteins associated with glucose metabolism and cellular motility. We also observed that MYB positively regulated the expression of four proteins with potential biomarker properties, i.e., FLNB, ENO1, ITGB1, and INHBA. Mining of publicly available databases using Oncomine and UALCAN demonstrated that these genes are overexpressed in pancreatic tumors and associated with reduced patient survival. Altogether, these data provide novel avenues for future investigations on diverse biological functions of MYB, specifically in the tumor microenvironment, and could also be exploited for biomarker development.

中文翻译：

蛋白质组学分析的MYB调节的分泌组确定功能途径和生物标记物：潜在的病理生物学和临床意义。

先前我们已经显示了MYB在胰腺肿瘤病理生物学中的重要作用。为了更好地了解MYB在肿瘤微环境中的作用并鉴定与MYB相关的分泌生物标记蛋白，我们对来自MYB调节和控制的胰腺癌细胞系中的分泌蛋白进行了质谱分析。我们还进行了计算机分析，以确定与MYB相关的生物功能，基因网络和改变的生物途径。我们的数据显示，MYB沉默的MiaPaCa细胞中337种分泌蛋白的显着调节（p <0.05），而过表达MYB的BxPC3细胞与它们各自的对照细胞相比，有282种蛋白存在差异。几种表型的改变，例如细胞运动，细胞死亡和存活，炎症反应，蛋白质合成等。与分泌组中MYB诱导的差异表达蛋白（DEP）相关。来自MYB沉默的MiaPaCa PC细胞的DEP提示主要与葡萄糖代谢，PI3K / AKT信号传导和氧化应激反应相关的基因下调。来自过表达MYB的BxPC3细胞的DEP表明与葡萄糖代谢和细胞运动有关的蛋白质释放增强。我们还观察到，MYB积极调节具有潜在生物标志物特性的四种蛋白质的表达，即FLNB，ENO1，ITGB1和INHBA。使用Oncomine和UALCAN挖掘可公开获得的数据库表明，这些基因在胰腺肿瘤中过表达，并且与患者生存率降低相关。共，

更新日期：2020-01-29

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