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免疫细胞富集的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 相互作用蛋白 USP13 的分子特征分析。

Molecular profiling of immune cell-enriched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacting protein USP13.

机构信息

Niğde Ömer Halisdemir University, Faculty of Medicine, Department of Medical Biology, Turkey.

出版信息

Life Sci. 2020 Oct 1;258:118170. doi: 10.1016/j.lfs.2020.118170. Epub 2020 Jul 29.

Abstract

AIMS

Coronavirus disease 2019 (COVID-19), which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a major health concern worldwide. Due to the lack of specific medication and vaccination, drug-repurposing attempts has emerged as a promising approach and identified several human proteins interacting with the virus. This study aims to provide a comprehensive molecular profiling of the immune cell-enriched SARS-CoV-2 interacting protein USP13.

MATERIALS AND METHODS

The list of immune cell-enriched proteins interacting with SARS-CoV-2 was retrieved from The Human Protein Atlas. Genomic alterations were identified using cBioPortal. Survival analysis was performed via Kaplan-Meier Plotter. Analyses of protein expression and tumor infiltration levels were carried out by TIMER.

KEY FINDINGS

14 human proteins that interact with SARS-CoV-2 were enriched in immune cells. Among these proteins, USP13 had the highest frequency of genomic alterations. Higher USP13 levels were correlated with improved survival in breast and lung cancers, while resulting in poor prognosis in ovarian and gastric cancers. Furthermore, copy number variations of USP13 significantly affected the infiltration levels of distinct subtypes of immune cells in head & neck, lung, ovarian and stomach cancers. Although our results suggested a tumor suppressor role for USP13 in lung cancer, in other cancers, its role seemed to be context-dependent.

SIGNIFICANCE

It is critical to identify and characterize human proteins that interact with SARS-CoV-2 in order to have a better understanding of the disease and to develop better therapies/vaccines. Here, we provided a comprehensive molecular profiling the immune cell-enriched SARS-CoV-2 interacting protein USP13, which will be useful for future studies.

摘要

目的

由严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)是全球主要的健康关注点。由于缺乏特定的药物和疫苗,药物再利用尝试已成为一种有前途的方法,并确定了几种与病毒相互作用的人类蛋白质。本研究旨在提供富含免疫细胞的 SARS-CoV-2 相互作用蛋白 USP13 的全面分子分析。

材料和方法

从人类蛋白质图谱中检索与 SARS-CoV-2 相互作用的富含免疫细胞的蛋白质列表。使用 cBioPortal 鉴定基因组改变。通过 Kaplan-Meier Plotter 进行生存分析。通过 TIMER 进行蛋白质表达和肿瘤浸润水平的分析。

主要发现

与 SARS-CoV-2 相互作用的 14 种人类蛋白质在免疫细胞中富集。在这些蛋白质中,USP13 的基因组改变频率最高。USP13 水平较高与乳腺癌和肺癌的生存改善相关,而在卵巢癌和胃癌中则预后不良。此外,USP13 的拷贝数变异显著影响头颈部、肺部、卵巢和胃部癌症中不同免疫细胞亚型的浸润水平。尽管我们的结果表明 USP13 在肺癌中起肿瘤抑制作用,但在其他癌症中,其作用似乎是上下文相关的。

意义

识别和表征与 SARS-CoV-2 相互作用的人类蛋白质对于更好地了解该疾病并开发更好的治疗方法/疫苗至关重要。在这里,我们提供了对富含免疫细胞的 SARS-CoV-2 相互作用蛋白 USP13 的全面分子分析,这将对未来的研究有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f300/7387267/4ac04e24f3cb/gr1_lrg.jpg

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