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基于 iTRAQ 的蛋白质组学分析揭示了人肾上腺皮质腺瘤中可能的靶相关蛋白。

ITRAQ-based proteomic analysis reveals possible target-related proteins in human adrenocortical adenomas.

机构信息

Department of Respiratory Medicine, the Second Hospital of Jilin University, Changchun, China.

Department of Anesthesiology, the Second Hospital of Jilin University, Changchun, China.

出版信息

BMC Genomics. 2019 Aug 16;20(1):655. doi: 10.1186/s12864-019-6030-5.

Abstract

BACKGROUND

Adrenocortical adenomas (ACAs) can lead to the autonomous secretion of aldosterone responsible for primary aldosteronism (PA), which is the most common form of secondary arterial hypertension. However, the authentic fundamental mechanisms underlying ACAs remain unclear.

OBJECTIVE

Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and bioinformatics analyses from etiological studies of ACAs were performed to screen the differentially expressed proteins (DEPs) and investigate the relevant mechanisms of their occurrence and development. Results could help determine therapeutic targets of clinical significance.

METHODS

In the present study, iTRAQ-based proteomics was applied to analyze ACA tissue samples from normal adrenal cortex tissues adjacent to the tumor. Using proteins extracted from a panel of four pairs of ACA samples, we identified some upregulated proteins and other downregulated proteins in all four pairs of ACA samples compared with adjacent normal tissue. Subsequently, we predicted protein-protein interaction networks of three DEPs to determine the authentic functional factors in ACA.

RESULTS

A total of 753 DEPs were identified, including 347 upregulated and 406 downregulated proteins. The expression of three upregulated proteins (E2F3, KRT6A, and ALDH1A2) was validated by Western blot in 24 ACA samples. Our data suggested that some DEPs might be important hallmarks during the development of ACA.

CONCLUSIONS

This study is the first proteomic research to investigate alterations in protein levels and affected pathways in ACA using the iTRAQ technique. Thus, this study not only provides a comprehensive dataset on overall protein changes but also sheds light on its potential molecular mechanism in human ACAs.

摘要

背景

肾上腺皮质腺瘤 (ACAs) 可导致醛固酮自主分泌,引起原发性醛固酮增多症 (PA),这是继发性动脉高血压最常见的形式。然而,ACAs 的确切根本机制尚不清楚。

目的

对来自 ACA 病因学研究的相对和绝对定量同位素标记 (iTRAQ)-基于蛋白质组学和生物信息学分析进行分析,以筛选差异表达蛋白 (DEPs) 并研究其发生和发展的相关机制。结果可能有助于确定具有临床意义的治疗靶点。

方法

本研究应用 iTRAQ 基于蛋白质组学分析了来自肿瘤旁正常肾上腺皮质组织的 ACA 组织样本。使用从四对 ACA 样本组成的蛋白质组学面板提取的蛋白质,我们鉴定了与相邻正常组织相比,所有四对 ACA 样本中一些上调的蛋白质和其他下调的蛋白质。随后,我们预测了三个 DEPs 的蛋白质-蛋白质相互作用网络,以确定 ACA 中的真实功能因素。

结果

共鉴定出 753 个 DEPs,包括 347 个上调和 406 个下调蛋白。在 24 个 ACA 样本中通过 Western blot 验证了三个上调蛋白 (E2F3、KRT6A 和 ALDH1A2) 的表达。我们的数据表明,一些 DEPs 可能是 ACA 发展过程中的重要标志。

结论

这项研究是使用 iTRAQ 技术首次进行的关于 ACA 中蛋白质水平变化和受影响途径的蛋白质组学研究。因此,本研究不仅提供了关于整体蛋白质变化的综合数据集,还揭示了其在人类 ACA 中的潜在分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e666/6697928/c24caf58d763/12864_2019_6030_Fig1_HTML.jpg

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