CCT4 suppression inhibits tumor growth in hepatocellular carcinoma by interacting with Cdc20

Li, Feng; Liu, Chunsheng; Ling, An-Sheng; Pan, Qi; Li, Xiaoning

doi:10.1097/cm9.0000000000001851

Cited by 12 publications

(10 citation statements)

References 29 publications

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“…27 For example, CCT4 can promote the proliferation and migration of HCC. 9 In the present study, we found that CCT4 was highly expressed in human ESCC cells and tissues, and was closely associated with poor prognosis, suggesting the important role of CCT4 in the tumorigenesis and progression of ESCC. Besides, CCT4 knockdown inhibited the growth, colony formation, and migration of ESCC cells.…”

Section: Discussionsupporting

confidence: 55%

“…CCT8 is highly expressed in glioma and further improves the proliferation and invasion of glioblastoma 8 . Similarly, upregulation of CCT4 promotes the proliferation, metastasis, invasion, and cell cycle progression of HCC cells 9 . Therefore, abnormal CCT expression is closely related to tumor formation and progression, which is expected to become potential cancer targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

“…8 Similarly, upregulation of CCT4 promotes the proliferation, metastasis, invasion, and cell cycle progression of HCC cells. 9 Therefore, abnormal CCT expression is closely related to tumor formation and progression, which is expected to become potential cancer targeted therapy. However, the expression and function of CCT4 in ESCC have not been reported.…”

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confidence: 99%

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CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

Fang

et al. 2022

Molecular Carcinogenesis

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Esophageal squamous cell carcinoma (ESCC) is a common human malignancy characterized by late-stage diagnosis, metastasis, and poor prognosis. Cisplatin (DDP)-based chemotherapy has been the most predominant treatment for patients with ESCC. However, the high rate of DDP resistance and toxicity seriously hinder its clinical application. Then, the optimized strategy and mechanisms for ESCC to enhance DDP sensitivity are in great demand. Accumulating evidence have shown that chaperone proteins are closely related to the tumorigenesis and drug resistance of cancers. Chaperonin containing TCP1 complex 4 (CCT4) is a recent identified member of the family. However, its expression and function in ESCC have not been well illustrated. In this study, we found that CCT4 was highly expressed in human ESCC tissues and cell lines, and closely related to the poor prognosis. Moreover, CCT4 silence raised oxidative stress and inhibited glycolysis of ESCC cells, which significantly inhibited cell proliferation and migration, promoted apoptosis and caused cell cycle arrest in ESCC cells. Interestingly, CCT4 knockdown enhanced the sensitivity of KYSE150 cells to DDP by regulating AMPK/AKT/Nrf2 signaling pathway and inhibiting glycolysis ability. Taken together, our results indicate that targeting CCT4 may be a therapeutic target in ESCC patients, which provides a theoretical basis to enhance the sensitivity of DDP in ESCC.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

Fang

et al. 2022

Molecular Carcinogenesis

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“…According to the sum of the correlations of these 385 genes in gastrointestinal cancer, we screened the 30 genes with the strongest correlations, which are RARS1, BTF3, HSPA4, NSA2, HNRNPA1, EIF3M, CCT4, OLA1, UIMC1, G3BP1, NACA, RSL1D1, ETF1, MRPS27, RBM22, CCT8, GEMIN5, LARS1, PA2G4, CDK7, NIFK, RSL24D1, EIF3E, THG1L, INTS13, UBE2D2, RPS23, DIMT1, RIOK2, and TTC27 respectively. Previous studies have reported that overexpression of BTF3, CCT8, CDK7, ELF3M, G3BP1, HSPA4, OLA1, and RSL1D1 can contribute to the occurrence and development of CRC ( Goh et al, 2011 ; Zhou et al, 2019 ; Zhou et al, 2021b ; Liao et al, 2021 ; Zhang et al, 2021 ; Liu et al, 2022a ; Liu et al, 2022b ; Li et al, 2022 ), overexpression of CCT4 and PA2G4 can contribute to the occurrence and development of LIHC( Li et al, 2021a ; Sun et al, 2022 ), overexpression of DIMT1 and HNRNPA1 can contribute to the occurrence and development of STAD ( Liu et al, 2017 ; Zhu et al, 2022 ), and overexpression of EIF3E and UIMC1 can contribute to the ESCA occurrence and development ( Xu et al, 2018 ; Yang et al, 2018 ). Therefore, we believe that these genes have the potential to be called diagnostic and therapeutic targets of gastrointestinal cancer.…”

Section: Discussionmentioning

confidence: 99%

Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis

Liu

Liu²,

Zeng³

et al. 2022

Front. Pharmacol.

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Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer.Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments.Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers.Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.

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“…NOP58 is not only negatively related to the OS of HCC patients, but may also be closely related to the recurrence of lung adenocarcinoma ( Shen et al, 2021 ; Wang et al, 2021 ). CCT4 is involved in protein metabolism and is significantly related to HCC cell growth and prognosis ( Li F. et al, 2021 ; Li W. et al, 2021 ). In addition, downregulation of CCT4 can significantly inhibit the migration of lung adenocarcinoma cells ( Tano et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

et al. 2022

Front. Genet.

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Background: This study aimed to screen potential drugs targeting a new prognostic gene signature associated with proliferation in hepatocellular carcinoma (HCC).Methods: CRISPR Library and TCGA datasets were used to explore differentially expressed genes (DEGs) related to the proliferation of HCC cells. Differential gene expression analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct a prognostic gene signature. Then the predictive power of the gene signature was validated in the TCGA and ICGC datasets. Furthermore, potential drugs targeting this gene signature were screened.Results: A total of 640 DEGs related to HCC proliferation were identified. Using univariate Cox analysis and random forest algorithm, 10 hub genes were screened. Subsequently, using multiplex combinatorial screening, five hub genes (FARSB, NOP58, CCT4, DHX37 and YARS) were identified. Taking the median risk score as a cutoff value, HCC patients were divided into high- and low-risk groups. Kaplan-Meier analysis performed in the training set showed that the overall survival of the high-risk group was worse than that of the low-risk group (p < 0.001). The ROC curve showed a good predictive efficiency of the risk score (AUC > 0.699). The risk score was related to gene mutation, cancer cell stemness and immune function changes. Prediction of immunotherapy suggetsted the IC50s of immune checkpoint inhibitors including A-443654, ABT-888, AG-014699, ATRA, AUY-922, and AZ-628 in the high-risk group were lower than those in the low-risk group, while the IC50s of AMG-706, A-770041, AICAR, AKT inhibitor VIII, Axitinib, and AZD-0530 in the high-risk group were higher than those in the low-risk group. Drug sensitivity analysis indicated that FARSB was positively correlated with Hydroxyurea, Vorinostat, Nelarabine, and Lomustine, while negatively correlated with JNJ-42756493. DHX37 was positively correlated with Raltitrexed, Cytarabine, Cisplatin, Tiotepa, and Triethylene Melamine. YARS was positively correlated with Axitinib, Fluphenazine and Megestrol acetate. NOP58 was positively correlated with Vorinostat and 6-thioguanine. CCT4 was positively correlated with Nerabine.Conclusion: The five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC.

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CCT4 suppression inhibits tumor growth in hepatocellular carcinoma by interacting with Cdc20

Abstract: Supplemental Digital Content is available in the text

Cited by 12 publications

References 29 publications

CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

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