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

Abstract

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.

Single cell RNA sequence combined with bulk RNA sequence to construct and validate a novel prognostic signature based on cell developmental trajectory- related genes to predict prognosis and immunotherapeutic response in Hepatocellular Carcinoma

“…Subsequently, we further con rmed the accuracy of the prognostic signature for predicting immunotherapy response using TIDE scores and external immunotherapy data Other investigations have corroborated the important genes involved in signature creation in our work. The proliferation rate, transition through the cell cycle, migration, and invasion were all reduced when CCT5 was knocked down in an HCC cell line, but elevated when CCT5 was overexpressed, as reported by Liu [25] . Shen [26] et al concluded that FLVCR1 was connected with the metabolism of HCC cells and that its overexpression predicted a bad prognosis for HCC patients.…”

Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer

“…In our study, CCT2 was highly expressed in 27 tumors, and this was confirmed by IHC results. In other studies, the expression levels of TRiC subunits TCP1, CCT2, CCT 3, CCT 4, CCT 5, CCT 6A, CCT 7, and CCT 8 were significantly upregulated in HCC (14). PAAD, READ, STAD, and UCEC are significantly upregulated in CCT2 expression than in adjacent normal tissues (9,15).…”

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status

“…The emergence of drug resistance and limited availability of inhibitors targeting multiple cell cycle modulators pose challenges that impede the ability to halt the uncontrolled growth of cancer, leading to malignancy. Although there are currently no clinically available inhibitors or drugs for CCT, the complex and its subunits have garnered increased attention in the eld of drug development 54,55 . Our study revealed that, among the nine CCT subunits, CCT6A showed the highest level of activation in colon cancer.…”