Exploring the Expression and Prognostic Value of the TCP1 Ring Complex in Hepatocellular Carcinoma and Overexpressing Its Subunit 5 Promotes HCC Tumorigenesis.

Exploring the Expression and Prognostic Value of the TCP1 Ring Complex in Hepatocellular Carcinoma and Overexpressing Its Subunit 5 Promotes HCC Tumorigenesis.
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探讨TCP1环复合物在肝细胞癌中的表达和预后价值及其亚基5过表达促进HCC肿瘤发生

DOI:
10.3389/fonc.2021.739660
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发表时间:
2021
影响因子:
4.7
通讯作者:
Sun Z
Sun Z
中科院分区:
医学3区
文献类型:
--
作者:
Liu J;Huang L;Zhu Y;He Y;Zhang W;Lei T;Xuan J;Xiao B;Li L;Zhou Q;Sun Z

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T复合体蛋白1环复合物(TRiC),也称为包含T复合体蛋白1(CCT)的伴侣蛋白,是新生蛋白质折叠所需的多亚基伴侣蛋白。越来越多的证据表明,TRiC也有助于肿瘤的发生和发展,但在肝细胞癌(HCC)中的致病功能的研究有限。我们使用The Cancer Genome Atlas和The Human Protein Atlas全面评估了TRiC亚基的表达模式和生物学功能。TRiC亚基TCP 1、CCT 2/3/4/5/6A/7/8在HCC组织中的表达水平在转录物和蛋白水平上均显著上调,这预测了较短的总生存期(OS)。此外,在几个CCT亚基中发现了高突变率,CCT基因改变的患者表现出较差的临床结局。功能富集分析表明,共调控基因主要参与“蛋白质折叠”和“基于微管的过程”,而与CCT亚基共表达的基因主要参与“核糖体”和“剪接体”。在HCC细胞系中,敲除CCT 5降低,而过表达增强增殖率、周期转换、迁移和侵袭。结论:TRiC亚基可能是HCC诊断的潜在生物标志物,在HCC的发生发展中起重要作用。
T-complex protein-1 ring complex (TRiC), also known as Chaperonin Containing T-complex protein-1 (CCT), is a multisubunit chaperonin required for the folding of nascent proteins. Mounting evidence suggests that TRiC also contributes to the development and progression of tumors, but there are limited studies on pathogenic functions in hepatocellular carcinoma (HCC). We comprehensively evaluated the expression pattern and biological functions of TRiC subunits using The Cancer Genome Atlas and The Human Protein Atlas. Expression levels of TRiC subunits TCP1, CCT2/3/4/5/6A/7/8 were significantly upregulated in HCC tissues at both transcript and protein levels, which predicted shorter overall survival (OS). Moreover, high mutation rates were found in several CCT subunits, and patients with altered CCT genes exhibited poorer clinical outcomes. Functional enrichment analysis showed that co-regulated genes were preferentially involved in ‘protein folding’ and ‘microtubule-based process’, while genes co-expressed with CCT subunits were primarily involved in ‘ribosome’ and ‘spliceosome’. Knockout of CCT5 in a HCC cell line reduced while overexpression enhanced proliferation rate, cycle transition, migration, and invasion. In conclusion, these findings suggest that subunits of the TRiC may be potential biomarkers for the diagnosis of HCC and play an important role in the occurrence and development of HCC.
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