Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

Dong, Zhao‐Ru; Zhou, Wei; Sun, Dong; Yan, Yu-Chuan; Yang, Chuncheng; Yang, Yafei; Li, Haichao; Zhi, Xu; Li, Tao

doi:10.7150/jca.37164

Cited by 6 publications

(4 citation statements)

References 29 publications

(40 reference statements)

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“…Thus, ZBTB16 may contribute to abnormal T cell development in MG, and ZBTB16 methylation is a potential mechanism of MG pathogenesis. WSB1, TRIM4, and RNF144b are associated with multiple cancers including neuroblastoma ( Shichrur et al, 2014 ), chordoma ( Wang C. B. et al, 2020 ) and hepatocellular carcinoma ( Dong et al, 2020 ). Abnormal methylation of TRIM4 in immune pathways may be associated with neural tube defects ( Zhang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of LINC00173 in Myasthenia Gravis by Integration Analysis of Aberrantly Methylated- Differentially Expressed Genes and ceRNA Networks

Wang

et al. 2021

Front. Genet.

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Myasthenia gravis (MG) is an autoimmune disease associated with autoantibody production that leads to skeletal muscle weakness. The molecular mechanisms underlying MG are not fully understood. We analyzed the gene expression profile (GSE85452) and methylation profile (GSE85647) of MG samples from the GEO database to identify aberrantly methylated-differentially expressed genes. By integrating the datasets, we identified 143 hypermethylation-low expression genes and 91 hypomethylation-high expression genes. Then we constructed PPI network and ceRNA networks by these genes. Phosphatase and tensin homolog (PTEN) and Abelson tyrosine-protein kinase (ABL)1 were critical genes in both PPI networks and ceRNA networks. And potential MG associated lncRNAs were selected by comprehensive analysis of the critical genes and ceRNA networks. In the hypermethylation-low expression genes associated ceRNA network, sirtuin (SIRT)1 was the most important gene and the lncRNA HLA complex (HC) P5 had the highest connection degree. Meanwhile, PTEN was the most important gene and the lncRNA LINC00173 had the highest connection degree in the hypomethylation-high expression genes associated ceRNA network. LINC00173 was validated to be upregulated in MG patients by qRT-PCR (P = 0.005), which indicated LINC00173 might be a potential biomarker for MG. These results provide a basis for future studies on the molecular pathogenesis of MG.

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Section: Discussionmentioning

confidence: 99%

Identification of LINC00173 in Myasthenia Gravis by Integration Analysis of Aberrantly Methylated- Differentially Expressed Genes and ceRNA Networks

Wang

et al. 2021

Front. Genet.

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“…ARRB1 has been indicated to promote HCC, and was upregulated by hepatitis B virus X protein (HBx) in mouse models [ 59 ]. Interestingly, among other candidate genes, some genes are related to the progression of HCC, including, GATAD1 [ 44 , 45 ], FOXK1 [ 46 ], RALGAPA2 [ 47 ], PDE4A [ 48 ], TRIP6 [ 49 ], SPTBN1 [ 53 ], PTP4A3 [ 54 ], TRIM4 [ 56 ], and LMNB1 [ 60 ]. These results suggest that the 36 candidate genes are associated with the functions of HBV and hepatocytes; however, this association needs to be further validated.…”

Section: Discussionmentioning

confidence: 99%

Identification of Therapeutic Targets for the Selective Killing of HBV-Positive Hepatocytes

Huang

Wang

2021

JPM

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The hepatitis B virus (HBV) infection is a major risk factor for cirrhosis and hepatocellular carcinoma. Most infected individuals become lifelong carriers of HBV as the drugs currently used to treat the patients can only control the disease, thereby achieving functional cure (loss of the hepatitis B surface antigen) but not complete cure (elimination of infected hepatocytes). Therefore, we aimed to identify the target genes for the selective killing of HBV-positive hepatocytes to develop a novel therapy for the treatment of HBV infection. Our strategy was to recognize the conditionally essential genes that are essential for the survival of HBV-positive hepatocytes, but non-essential for the HBV-negative hepatocytes. Using microarray gene expression data curated from the Gene Expression Omnibus database and the known essential genes from the Online GEne Essentiality database, we used two approaches, comprising the random walk with restart algorithm and the support vector machine approach, to determine the potential targets for the selective killing of HBV-positive hepatocytes. The final candidate genes list obtained using these two approaches consisted of 36 target genes, which may be conditionally essential for the cell survival of HBV-positive hepatocytes; however, this requires further experimental validation. Therefore, the genes identified in this study can be used as potential drug targets to develop novel therapeutic strategies for the treatment of HBV, and may ultimately help in achieving the elusive goal of a complete cure for hepatitis B.

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“…[ 15 ] The TRIM family member TRIM4 has recently been shown to be involved in the virus‐induced IFN production, [ 16 ] oxidative stress‐induced cell death, [ 17 ] and hepatocellular carcinoma. [ 18 ] The functional importance of TRIM4 in breast cancer, however, has yet to be established.…”

Section: Introductionmentioning

confidence: 99%

The E3 Ligase TRIM4 Facilitates SET Ubiquitin‐Mediated Degradation to Enhance ER‐α Action in Breast Cancer

et al. 2022

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Estrogen receptor alpha (ER‐α) action is critical for hormone‐dependent breast cancer, and ER‐α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)‐resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER‐α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4‐SET interactions are mediated by the RING and B‐box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48‐linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence‐free survival outcomes in patients with ER‐α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients.

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Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

Cited by 6 publications

References 29 publications

Identification of LINC00173 in Myasthenia Gravis by Integration Analysis of Aberrantly Methylated- Differentially Expressed Genes and ceRNA Networks

Identification of LINC00173 in Myasthenia Gravis by Integration Analysis of Aberrantly Methylated- Differentially Expressed Genes and ceRNA Networks

Identification of Therapeutic Targets for the Selective Killing of HBV-Positive Hepatocytes

The E3 Ligase TRIM4 Facilitates SET Ubiquitin‐Mediated Degradation to Enhance ER‐α Action in Breast Cancer

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