EWS-FLI1 positively regulates autophagy by increasing ATG4B expression in Ewing sarcoma cells

Lu, Qiong; Zhang, Yuankai; Ma, Liang; Li, Deqiang; Li, Ming; Li, Jianmin; Liu, Peilai

doi:10.3892/ijmm.2017.3112

Cited by 11 publications

(14 citation statements)

References 49 publications

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“…Autophagy plays great roles in the clearance of longlived proteins, aggregates and damaged organelles, and dysregulation of autophagy is highly associated with cancer, particularly in tumorigenesis and chemotherapy resistance. 13 In the current study, we found that TRIM3 could regulate autophagy in ES cells. Overexpression of TRIM3 significantly inhibits autophagy, as evidenced by the increases in the amount of P62 (SQSTM1) and decreases in the amount of LC3B-II, two important markers of autophagy, as well as the increased LC3 puncta in cells.…”

Section: Discussionmentioning

confidence: 50%

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<p>TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells</p>

Lu¹,

Zhang²,

Ma³

et al. 2019

OTT

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Background and aim: Ewing sarcoma (ES) is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. In the current study, we were aiming to investigate the function of TRIM3 in autophagy in ES cells. Methods: The expression of TRIM3 in Ewing sarcoma tissues and normal tissues was examined by quantitative PCR and western blot. The effect of TRIM3 on autophagy was detected by western blot and immunofluorescence assay. Target of TRIM3 was examined by western blot, immunoprecipitation and ubiquitination assay. Results: We found the expression of TRIM3 was significantly up-regulated in Ewing sarcoma tissues compared with normal tissues, and this phenomenon was regulated by EWS-FLI1 expression. Furthermore, we observed that overexpression of TRIM3 markedly and consistently inhibited autophagy in ES cells, and autophagy was enhanced in TRIM3silenced ES cells. Finally, we found in ES cells, TRIM3 could directly interact with Beclin1, and improved its K48-linked polyubiquitinaion, leading to the degradation of Beclin1 and then regulated autophagy. Conclusion: In the present research, for the first time we revealed that TRIM3 negatively regulates autophagy through promoting degradation of Beclin1 in Ewing sarcoma cells, and these findings may provide ideas for ES research.

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Section: Discussionmentioning

confidence: 50%

“…In previous study, we found that EWS-FLI1 promotes autophagy in ES cells, 13 therefore we supposed if TRIM3 could also regulate autophagy. Overexpression of TRIM3 in TC71 cells was confirmed as shown in Figure 3A.…”

Section: Overexpression Of Trim3 Inhibited Autophagy In Es Cellsmentioning

confidence: 89%

<p>TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells</p>

Lu¹,

Zhang²,

Ma³

et al. 2019

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“…The translocation fusion between EWS and ETS family members produces a potent oncogenic transcription factor 177 capable of inducing tumorigenesis through increased cell viability and proliferation, 178 – 181 apoptosis inhibition, 180 metabolic changes to favor biosynthesis, and subsequent cell division. 182 EWS – ETS regulates cell proliferation and anchorage-independent growth in ES cells, but not in a non-ES cell line.…”

Section: Ewing’s Sarcomamentioning

confidence: 99%

“… 181 Additionally, EWS – ETS induces autophagy in ES through overexpression of an autophagy-related gene, ATG4B , which leads to a higher rate of proliferation and lower rate of apoptosis. 180 Metabolism in ES is also altered due to EWS – ETS oncogenic regulation, which increases serine biosynthesis via PGHDH upregulation, for the production of proteins, lipids, and nucleic acids to meet the demands of cell proliferation. 182 Interestingly, elevated PGHDH expression is highest in ES compared to other cancer cell lines, as well as normal tissue, and patients who are deemed at high risk show upregulation in PGHDH.…”

Section: Ewing’s Sarcomamentioning

confidence: 99%

A review of soft-tissue sarcomas: translation of biological advances into treatment measures

Hoang¹,

Acevedo²,

Mann³

et al. 2018

CMAR

107

176

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Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease.

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“…In the past studies of ES, it has been reported that autophagy-related genes are closely related to the development of ES. For example, TRIM3 negatively regulates autophagy by promoting the degradation of Beclin1 in ES cells, eWS-FLI1 actively regulates autophagy by increasing the expression of ATG4B in ES cells [11]. However, the relationship between autophagy-related genes and the prognosis of ES patients is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Implications of Autophagy-Related Gene Signatures in Ewing’s Sarcoma

Zhou¹,

Wu²,

Liu³

et al. 2021

Preprint

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Backgrand：Ewing's sarcoma (ES) is a highly aggressive malignant bone tumor with a high incidence among children and adolescents. While autophagy often plays an important role in tumor development species, we developed an autophagy-related prognostic signature based on the GEO dataset.Methods: Using the GEO database with the online website Human Autophagy Database(HADb), we screened for autophagy-related differential genes and we performed enrichment analysis and PPI analysis for autophagy-related differential genes, and then, constructed our autophagy-related prognostic gene signature by univariate Cox regression, lasso regression, and multivariate Cox regression .Results: We screened a total of 72 autophagy-related differential genes, and a total of 8 autophagy-related prognostic genes were screened by machine learning algorithms. ROC curves and survival curves also showed good predictive power of the 8 gene signatures. In addition, univariate and multivariate cox regression also showed that the 8 gene signatures were independent prognostic factors. And the results of GSEA enrichment analysis also revealed the correlation between autophagy and metabolic pathways.Conlusion：In summary, we developed an autophagy-related mRNA signature consisting of 8 mRNAs that effectively classified ES patients into low- and high-risk groups. The application of the signature in clinical treatment needs further observation to validate the validity of our findings.

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EWS-FLI1 positively regulates autophagy by increasing ATG4B expression in Ewing sarcoma cells

Cited by 11 publications

References 49 publications

<p>TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells</p>

<p>TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells</p>

A review of soft-tissue sarcomas: translation of biological advances into treatment measures

Prognostic Implications of Autophagy-Related Gene Signatures in Ewing’s Sarcoma

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