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The TCP1 ring complex is associated with malignancy and poor prognosis in hepatocellular carcinoma
Liheng Yao1, Xuejing Zou1, Li Liu1
1Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University Guangzhou, Guangdong Province, P. R. China.
Abstract:
TCP1 ring complex (TRiC) participates in protein folding in cells, regulating the expression of many tumor-related proteins and the cell cycle. Although the clinical significance of its subunits has been widely discussed in various malignancies, limited studies have explored its function in hepatocellular carcinoma (HCC) in the perspective of a complex. This study discusses the clinical significance of the TRiC subunits in HCC patients in terms of expression level, prognostic value, and potential mechanism. We used HCC samples from Nanfang hospital, data from The Cancer Genome Atlas (TCGA) database and information from the Gene Expression Omnibus (GEO) database with statistical methods and Gene Set Enrichment Analysis (GSEA) to analyze the gene expression levels of TRiC subunits along with survival data. We found altered expressions of the TRiC subunits in HCC, including significantly increased TCP1/CCT2/CCT3/CCT4/CCT5/CCT6A/CCT7/CCT8 expressions as well as decreased CCT6B expression, which predict poor prognosis and are associated with tumor progression. Moreover, the expression levels of these genes were pairwise correlated in HCC, indicating that the function of the entire complex should be explored as a functional macrocosm. Finally, we identified that the overexpressions of TCP1/CCT2/CCT3/CCT4/CCT5/CCT6A are involved in the dysregulation of Myc target genes, hypoxia-inducible factor (HIF) target genes and cell cycle especially the G1/S transition. Our study found that all TRiC subunits are aberrantly co-expressed in HCC, and these components have potential as therapeutic targets.
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