TCOF1 coordinates oncogenic activation and rRNA production and promotes tumorigenesis in HCC

Wu, Chaoshen; Xia, Dian; Wang, Dian; Wang, Shu; Sun, Zhaoran; Xu, Bihuai; Zhang, Daoyong

doi:10.1111/cas.15242

Cited by 22 publications

(22 citation statements)

References 21 publications

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“…In summary, they suggest that upregulation of Treacle expression promotes carcinogenesis, stimulates proliferation, survival, and possibly contributes to radio-resistance, albeit with variation across different cancer types ( Figure 2 ). We observe significant upregulation of Treacle expression in 11 out of 14 different cancer types by analysis of paired normal and tumor data in agreement with other recently published studies ( Wu et al, 2021 ; Gu et al, 2022 ; Hu et al, 2022 ). Interestingly, in uterine corpus endometrial carcinoma, where Treacle expression was not increased, the highest frequency of TCOF1 mutations were identified by Gu et al, 2022 , possibly altering the properties of the expressed protein.…”

Section: Discussionsupporting

confidence: 93%

“…Several recent studies focusing on the prognostic and potential therapeutic value of Treacle in cancer reach conclusions in agreement with our data. Wu et al proposed a role for Treacle in oncogenic activation and promotion of tumorigenesis in human hepatocellular carcinoma (HCC) ( Wu et al, 2021 ). They found a positive correlation between Treacle expression levels and advanced pathological stages and histological grade in HCC, suggesting a role for Treacle in cancer progression.…”

Section: Introductionmentioning

confidence: 99%

“…They found a positive correlation between Treacle expression levels and advanced pathological stages and histological grade in HCC, suggesting a role for Treacle in cancer progression. In addition, they found that high Treacle expression resulted in a significant decrease in overall survival probability in HCC patients ( Wu et al, 2021 ). This data is in agreement with the RNA-seq data analyzed here, showing a significant upregulation of Treacle expression in liver cancer as well as a significant correlation between high Treacle expression and poor survival ( Wu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence of Treacle overexpression in cancer raises the prospect of targeting Treacle as a novel anti-cancer strategy. The cellular response to Treacle silencing supports this approach ( Wu et al, 2021 ), as does its role in both ribosome biogenesis and DNA repair.…”

Section: Introductionmentioning

confidence: 99%

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Treacle is Upregulated in Cancer and Correlates With Poor Prognosis

Oxe

Larsen

2022

Front. Cell Dev. Biol.

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Treacle/TCOF1 is an adaptor protein specifically associated with nucleolar chromatin. In the nucleolus it stimulates ribosome biogenesis, thereby promoting growth and proliferation. A second role of Treacle has emerged as a coordinator of the nucleolar responses to DNA damage, where it facilitates nucleolar DNA repair and cellular survival after genotoxic insults. The involvement of Treacle in multiple fundamental processes such as growth, proliferation, and genome stability, which are tightly linked to cancer, raises the question of Treacle’s role in the development of this disease. On one hand, overexpression of Treacle could stimulate nucleolar transcription and ribosome biogenesis providing a growth advantage in cancer cells. On the other hand, the function of Treacle as a gatekeeper in response to nucleolar DNA damage could favor mutations that would impair its function. In this perspective, we analyze paired Treacle expression data from the Cancer Genome Atlas (TCGA) and correlate expression with patient survival in different cancer types. We also discuss other recently published observations of relevance to the role of Treacle in cancer. In light of these new observations, we propose possible roles of Treacle in carcinogenesis and discuss its potential as a therapeutic target.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treacle is Upregulated in Cancer and Correlates With Poor Prognosis

Oxe

Larsen

2022

Front. Cell Dev. Biol.

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“…Treacle upregulation is however emerging as a tumor promoting factor. Elevated Treacle levels correlated with poor prognosis, and shorter survival in different cancer types ( Gu et al, 2022 ; Hu et al, 2022 ; Wu et al, 2022 ). This could be attributed to Treacle’s function in facilitating rRNA transcription.…”

Section: Treacle In Cancermentioning

confidence: 99%

Treacle Sticks the Nucleolar Responses to DNA Damage Together

Gál

Nieto

Boukoura

et al. 2022

Front. Cell Dev. Biol.

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The importance of chromatin environment for DNA repair has gained increasing recognition in recent years. The nucleolus is the largest sub-compartment within the nucleus: it has distinct biophysical properties, selective protein retention, and houses the specialized ribosomal RNA genes (collectively referred to as rDNA) with a unique chromatin composition. These genes have high transcriptional activity and a repetitive nature, making them susceptible to DNA damage and resulting in the highest frequency of rearrangements across the genome. A distinct DNA damage response (DDR) secures the fidelity of this genomic region, the so-called nucleolar DDR (n-DDR). The composition of the n-DDR reflects the characteristics of nucleolar chromatin with the nucleolar protein Treacle (also referred to as TCOF1) as a central coordinator retaining several well-characterized DDR proteins in the nucleolus. In this review, we bring together data on the structure of Treacle, its known functions in ribosome biogenesis, and its involvement in multiple branches of the n-DDR to discuss their interconnection. Furthermore, we discuss how the functions of Treacle in ribosome biogenesis and in the n-DDR may contribute to Treacher Collins Syndrome, a disease caused by mutations in Treacle. Finally, we outline outstanding questions that need to be addressed for a more comprehensive understanding of Treacle, the n-DDR, and the coordination of ribosome biogenesis and DNA repair.

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A Novel Amino Acid‐Related Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma

Wang,

Huang,

et al. 2024

Cancer Reports

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Background and AimsHepatocellular carcinoma (HCC) is an extremely harmful malignant tumor in the world. Since the energy metabolism and biosynthesis of HCC cells are closely related to amino acids, it is necessary to further explore the relationship between amino acid‐related genes and the prognosis of HCC to achieve individualized treatment. We herein aimed to develop a prognostic model for HCC based on amino acid genes.MethodsIn this study, RNA‐sequencing data of HCC patients were downloaded from the TCGA‐LIHC cohort as the training cohort and the GSE14520 cohort as the validation cohort. Amino acid‐related genes were derived from the Molecular Signatures Database. Univariate Cox and Lasso regression analysis were used to construct an amino acid‐related signature (AARS). The predictive value of this risk score was evaluated by Kaplan–Meier (K–M) curve, receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression analysis. Gene set variation analysis (GSVA) and immune characteristics evaluation were used to explore the underlying mechanisms. Finally, a nomogram was established to help the personalized prognosis assessment of patients with HCC.ResultsThe AARS comprises 14 amino acid‐related genes to predict overall survival (OS) in HCC patients. HCC patients were divided into AARS‐high group and AARS‐low group according to the AARS scores. The K–M curve, ROC curve, and univariate and multivariate Cox regression analysis verified the good prediction efficiency of the risk score. Using GSVA, we found that AARS variants were concentrated in four pathways, including cholesterol metabolism, delayed estrogen response, fatty acid metabolism, and myogenesis metabolism.ConclusionOur results suggest that the AARS as a prognostic model based on amino acid‐related genes is of great value in the prediction of survival of HCC, and can help improve the individualized treatment of patients with HCC.

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TCOF1 coordinates oncogenic activation and rRNA production and promotes tumorigenesis in HCC

Cited by 22 publications

References 21 publications

Treacle is Upregulated in Cancer and Correlates With Poor Prognosis

Treacle is Upregulated in Cancer and Correlates With Poor Prognosis

Treacle Sticks the Nucleolar Responses to DNA Damage Together

A Novel Amino Acid‐Related Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma

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