&lt;p&gt;TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells&lt;/p&gt;

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

doi:10.2147/ott.s219777

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…For example, Lys (K) 63linked ubiquitination modulated by Ube2v1 expression enhanced protein aggregation and contributed to Ube2v1's function in regulating protein aggregate formation [30]. However, TRIM3 could directly interact with Beclin1, and improved its K48-linked polyubiquitination, leading to the degradation of Beclin1 and then regulated autophagy [31]. We further demonstrated that UBE2T functions as a tumour promoter in GBM by maintaining the protein level of GRP78.…”

Section: Agingmentioning

confidence: 78%

UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT

Huang

Guo

Zhao

et al. 2020

Aging

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Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial- mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.

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Section: Agingmentioning

confidence: 78%

UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT

Huang

Guo

Zhao

et al. 2020

Aging

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“…However, the survival rates of patients with metastasis and recurrence are still unacceptable low [2]. To date, accumulating evidences suggest a close relationship between autophagy and ES [21][22][23][24][25][26][27][28]. Here, our finding that ATG2B, ATG10 and DAPK1 are potential protective ARGs with prognostic value in ES is valuable.…”

Section: Discussionmentioning

confidence: 69%

“…There were also many reports indicating that ATG2B was associated with drug resistance by activating autophagy in multiple tumors [10,11]. Although ATG2B had not been reported in ES, but there had been plenty of reports that autophagy was associated with the prognosisi of ES [19][20][21][22][23][24][25][26]. In our study, ATG2B was found to be a potential protective factor in ES, the same as it's in gastric and colorectal carcinomas, breast carcinoma and cutaneous squamous cell carcinoma, but opposite to non-small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

2022

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Background Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it’s necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. Results ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. Conclusions ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

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“…TRIM proteins have been associated with many biological processes, including transcriptional regulation cell differentiation, signaling transduction, and apoptosis. Overexpression of TRIM3 significantly inhibits autophagy through promoting the degradation of Beclin-1, as evidenced by the increases in the amount of P62 (SQSTM1) and the reductions in the amount of LC3B-II, two important markers of autophagy, as well as by the increased LC3 puncta in cells [68].…”

Section: The Impact Of Autophagy In Ewing Sarcomamentioning

confidence: 99%

The Controversial Role of Autophagy in Ewing Sarcoma Pathogenesis—Current Treatment Options

et al. 2021

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Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) and FLI1 (Friend leukemia virus integration site 1) genes, leading to an EWS–FLI1 fused protein, which is associated with autophagy, a homeostatic and catabolic mechanism under normal and pathological conditions. Following such interesting and controversial data regarding autophagy in ES, many clinical trials using modulators of autophagy are now underway in this field. In the present review, we summarize current data and clinical trials that associate autophagy with ES. In vitro studies highlight the controversial role of autophagy as a tumor promoter or a tumor suppressor mechanism in ES. Clinical and in vitro studies on ES, together with the autophagy modulators, suggest that caution should be adopted in the application of autophagy as a therapeutic target. Monitoring and targeting autophagy in every ES patient could eliminate the need for targeting multiple pathways in order to achieve the maximum beneficial effect. Future studies are required to focus on which ES patients are affected by autophagy modulators in order to provide novel and more efficient therapeutic protocols for patients with ES based on the current autophagy status of the tumors.

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

Cited by 8 publications

References 24 publications

UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT

UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

The Controversial Role of Autophagy in Ewing Sarcoma Pathogenesis—Current Treatment Options

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