Overexpression of EWSR1 (Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1) predicts poor survival in patients with hepatocellular carcinoma

Jiang, Weijie; Wu, Tao; Shi, Xuan; Xu, Jiawen

doi:10.1080/21655979.2021.1982844

Cited by 7 publications

(4 citation statements)

References 33 publications

(31 reference statements)

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“…CPSF6 is able to upregulate NQO1 to regulate HCC cell metabolism and thereby promote tumor development [ 61 ]. EWSR1 is strongly expressed in HCC, it is associated with histological grade and pathological T stage, and it is considered a novel tumor prognostic marker [ 62 ]. HSP90AB1 is also associated with HCC, and it may be involved in the progression from cirrhosis to HCC [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis Reveals the Potential Role and Prognostic Value of GOLM1 in Hepatocellular Carcinoma

Lin

Gao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Overexpression of Golgi membrane protein 1 (GOLM1) is closely associated with hepatocellular carcinoma (HCC) vascular invasion. How GOLM1 may be involved in angiogenesis in HCC remains unclear. We explored how GOLM1 promotes angiogenesis in HCC and potential prognostic value. Expression levels of GOLM1 in HCC patients and healthy controls were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) between HCC patients and controls were compared. GOLM1 was knocked out in the HCC cell line, and RNA sequencing and DEG expression analysis were performed compared with control cells. Based on TCGA data and cell line RNA sequencing data, DEGs affected by a high expression of GOLM1 were identified. Subsequently, enrichment analysis was performed to explore the functions and pathways of the DEGs affected by a high expression of GOLM1. A relevant network analysis was built. Cox regression, genomic variance analysis scores, minimum absolute shrinkage and selection operator regression, and random forest regression models were applied to determine the best prognostic model and validated using the GSE54236 dataset from the Gene Expression Omnibus (GEO). We determined the effect of GOLM1 expression on immune cell infiltration in liver cancer. GOLM1 was overexpressed in HCC tissues compared with controls, and its level correlated with tumor purity and prognosis. 400 DEGs affected by highly expressed GOLM1 were identified in TCGA and cell line RNA sequencing data. Enrichment analysis revealed that these DEGs may be related to biological processes of oxidative stress and angiogenesis and involved in the VEGF signaling pathway and protein processing in endoplasmic reticulum. We predicted a comprehensive regulatory network in which GOLM1 activated VEGF signaling to promote HCC angiogenesis. GOLM1 may interact with E2F1 and IGF2BP3 to promote angiogenesis. GOLM1 overexpression was associated with greater immune cell infiltration. A random forest regression model was the best prognostic model. Our study reveals a potential molecular mechanism of GOLM1 in promoting HCC. We developed two prognostic models based on DEG associated with GOLM1 overexpression to help stratify HCC prognosis and improve individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Integrative Analysis Reveals the Potential Role and Prognostic Value of GOLM1 in Hepatocellular Carcinoma

Lin

Gao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…It is widely noted that several genes are capable of being applied as promising diagnostic and prognostic biomarkers for HCC ( Jiang W. et al, 2021 ; Zhou et al, 2021 ). The association of identified TRIMs with clinicopathological factors and the prognosis of HBV-associated HCC was investigated.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of TRIM Family Genes in Hepatitis Virus B-Related Hepatoma Carcinoma

Li²,

Li³

et al. 2022

Front. Genet.

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Background: As significant components of E3 ligases, the tripartite motif (TRIM) proteins participate in various biological processes and facilitate the development of several diseases. Nevertheless, the correlations of TIRMs with hepatitis B virus (HBV)-positive hepatoma carcinoma (HCC) are not well elaborated.Methods: The expression profile of TRIM genes in HBV-associated HCC and related clinical information were extracted from the Cancer Genome Atla (TCGA) database and the International Cancer Genome Consortium (ICGC) database. Dependent on the ConsensusPathDB and STRING databases, the gene ontology, Reactome pathways, and protein-protein interaction were assessed. Relied on TIMER 2.0 database, the relationship of the TRIMs with immune infiltration was investigated. Using multivariate analysis and Kaplan Meier analysis, the association between TRIM genes and the prognostic value was examined.Results: A total of 17 TRIM genes, including TRIM16, TRIM17, and TRIM31 with fold change no less than 1.5, were discovered to upregulate in HBV-associated HCC in both TCGA and ICGC cohorts. Relied on gene enrichment analysis, the identified TRIMs were observed to not only be related to the interferon and cytokine signaling but also linked to the adaptive immune system. Particularly, the co-expression patterns of identified TRIMs with other E3 ligase genes and many innate immune genes that are associated with Toll-like receptor signaling, apoptosis, and SUMOylation. Besides, some of identified TRIM expressions were also linked to the infiltration levels of T cells and B cells. Additionally, several TRIM genes were associated with various clinical factors and relevant to the poor survival of HBV-associated HCC.Conclusion: Our findings could deepen our understanding of TRIMs and their correlations with HBV-associated HCC. Furthermore, some of these TRIMs may be utilized as new prognostic markers of HBV-related HCC prognosis, or act as potential molecular targets for the disease.

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“…Jiang W et al revealed that EWSR1 may be related to the regulation of mRNA processing in HCC. [31] Therefore, we hypothesized that the changes in PPARA and FABP1 expression induced by LINC01116 knockdown might be due to the effect of EWSR1 on their mRNA levels. First, we confirmed that the knockdown of EWSR1 in Hep-3B and HCCLM3 cells resulted in decreased mRNA and protein levels of PPARA and FABP1.…”

Section: Linc01116 Plays a Cancer-promoting Role Through The Ewsr1/pp...mentioning

confidence: 99%

Hepatocellular Carcinoma LINC01116 Outcompetes T Cells for Linoleic Acid and Accelerates Tumor Progression

Ma,

Chu,

Liu

et al. 2024

Advanced Science

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a highly immunosuppressive tumor microenvironment and a typical pattern of disturbances in hepatic lipid metabolism. Long non‐coding RNAs are shown to play an important role in the regulation of gene expression, but much remains unknown between tumor microenvironment and lipid metabolism as a bridging molecule. Here, long intergenic nonprotein coding RNA 01116 (LINC01116) acts as this molecular which is frequently upregulated in HCC patients and associated with HCC progression in vitro and in vivo is identified. Mechanistically, LINC01116 stabilizes EWS RNA‐binding protein 1 (EWSR1) by preventing RAD18 E3 Ubiquitin Protein Ligase (RAD18) ‐mediated ubiquitination. The enhanced EWSR1 protein upregulates peroxisome proliferator activated receptor alpha (PPARA) and fatty acid binding protein1 (FABP1) expression, a long‐chain fatty acid (LCFA) transporter, and thus cancer cells outcompete T cells for LCFAs, especially linoleic acid, for seeding their own growth, leading to T cell malfunction and HCC malignant progression. In a preclinical animal model, the blockade of LINC01116 leads to enhanced efficacy of anti‐PD1 treatment accompanied by increased cytotoxic T cell and decreased exhausted T cell infiltration. Collectively, LINC01116 is an immunometabolic lncRNA and the LINC01116‐EWSR1‐PPARA‐FABP1 axis may be targetable for cancer immunotherapy.

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Overexpression of EWSR1 (Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1) predicts poor survival in patients with hepatocellular carcinoma

Cited by 7 publications

References 33 publications

Integrative Analysis Reveals the Potential Role and Prognostic Value of GOLM1 in Hepatocellular Carcinoma

Integrative Analysis Reveals the Potential Role and Prognostic Value of GOLM1 in Hepatocellular Carcinoma

Comprehensive Analysis of TRIM Family Genes in Hepatitis Virus B-Related Hepatoma Carcinoma

Hepatocellular Carcinoma LINC01116 Outcompetes T Cells for Linoleic Acid and Accelerates Tumor Progression

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