<br>CDK1-SRC 相互作用依赖性 HSP90AB1 转录激活促进肝细胞癌的抗肿瘤免疫,Journal of Proteome Research

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CDK1-SRC 相互作用依赖性 HSP90AB1 转录激活促进肝细胞癌的抗肿瘤免疫
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2023-11-10 , DOI: 10.1021/acs.jproteome.3c00379
Yi-Jie Zhang _{1,

2} , De-Hui Yi _{1,

2}

Affiliation

本研究旨在分析多组学数据并构建涉及肝细胞癌（HCC）预后的激酶、转录因子和免疫基因的调控网络。研究人员使用来自 TCGA 和 GEO 数据库的转录组、蛋白质组和临床数据来识别与 HCC 相关的免疫基因。进行统计分析、荟萃分析和蛋白质-蛋白质相互作用分析，以确定关键的免疫基因及其关系。体外和体内实验验证了 CDK1-SRC-HSP90AB1 网络对 HCC 进展和抗肿瘤免疫的影响。利用临床病理学特征和免疫浸润开发了预后风险模型。免疫基因 LPA、BIRC5、HSP90AB1、ROBO1 和 CCL20 被确定为关键预后因素。 CDK1-SRC-HSP90AB1 网络促进 HCC 细胞增殖和迁移，其中 HSP90AB1 通过 CDK1-SRC 相互作用进行转录激活。操纵 SRC 或 HSP90AB1 可逆转 CDK1 和 SRC 对 HCC 的影响。 CDK1-SRC-HSP90AB1网络还影响HCC肿瘤形成和抗肿瘤免疫。总体而言，这项研究强调了 CDK1-SRC-HSP90AB1 网络作为 HCC 预后中至关重要的免疫调节网络的重要性。

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CDK1-SRC Interaction-Dependent Transcriptional Activation of HSP90AB1 Promotes Antitumor Immunity in Hepatocellular Carcinoma

This study aimed to analyze multiomics data and construct a regulatory network involving kinases, transcription factors, and immune genes in hepatocellular carcinoma (HCC) prognosis. The researchers used transcriptomic, proteomic, and clinical data from TCGA and GEO databases to identify immune genes associated with HCC. Statistical analysis, meta-analysis, and protein–protein interaction analyses were performed to identify key immune genes and their relationships. In vitro and in vivo experiments validated the CDK1-SRC-HSP90AB1 network’s effects on HCC progression and antitumor immunity. A prognostic risk model was developed using clinicopathological features and immune infiltration. The immune genes LPA, BIRC5, HSP90AB1, ROBO1, and CCL20 were identified as the key prognostic factors. The CDK1-SRC-HSP90AB1 network promoted HCC cell proliferation and migration, with HSP90AB1 being transcriptionally activated by the CDK1–SRC interaction. Manipulating SRC or HSP90AB1 reversed the effects of CDK1 and SRC on HCC. The CDK1-SRC-HSP90AB1 network also influenced HCC tumor formation and antitumor immunity. Overall, this study highlights the importance of the CDK1-SRC-HSP90AB1 network as a crucial immune-regulatory network in the HCC prognosis.

更新日期：2023-11-10

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