Nrdp1S, short variant of Nrdp1, inhibits human glioma progression by increasing Nrdp1‐mediated ErbB3 ubiquitination and degradation

Wu, Yuxuan; Wang, Lei; Bao, Hanmo; Zou, Shenshan; Fu, Chunling; Gong, Hui; Gao, Yong; Tang, Yuan; Yu, Rutong; Shi, Hengliang

doi:10.1111/jcmm.12735

Cited by 12 publications

(8 citation statements)

References 28 publications

(51 reference statements)

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“…The degradation of intracellular proteins is mainly accomplished by the ubiquitin-proteasome system, and the ubiquitin-proteasome have strong selectivity for protein degradation [ 23 ]. Studies have shown that the ubiquitination pathway is closely related to the occurrence and development of tumors [ 1 , 2 , 8 , 9 , 19 ]. Here we identified six differentially expressed URGs that were related to survival in glioma patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

et al. 2021

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Ubiquitination is a dynamic and reversible process of a specific modification of target proteins catalyzed by a series of ubiquitination enzymes. Because of the extensive range of substrates, ubiquitination plays a crucial role in the localization, metabolism, regulation, and degradation of proteins. Although the treatment of glioma has been improved, the survival rate of patients is still not satisfactory. Therefore, we explore the role of ubiquitin proteasome in glioma. Survival-related ubiquitination related genes (URGs) were obtained through analysis of the Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA). Cox analysis was performed to construct risk model. The accuracy of risk model is verified by survival, Receiver operating characteristic (ROC) and Cox analysis. We obtained 36 differentially expressed URGs and found that 25 URGs were related to patient prognosis. We used the 25 URGs to construct a model containing 8 URGs to predict glioma patient risk by Cox analysis. ROC showed that the accuracy rate of this model is 85.3%. Cox analysis found that this model can be used as an independent prognostic factor. We also found that this model is related to molecular typing markers. Patients in the high-risk group were enriched in multiple tumor-related signaling pathways. In addition, we predicted TFs that may regulate the risk model URGs and found that the risk model is related to B cells, CD4 T cells, and neutrophils.

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Section: Discussionmentioning

confidence: 99%

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

et al. 2021

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“…In a previous study, we have shown that Nrdp1 is implicated in ischemic cardiomyocyte death, in which overexpression of Nrdp1 augmented ischemia–reperfusion (I/R)-induced cardiomyocyte apoptosis while inhibition of endogenous Nrdp1 could protect cardiomyocytes against I/R injury (Zhang et al, 2011b ). In the brain, Nrdp1 is found to be involved in suppressing brain tumor formation and promoting lipopolysaccharide (LPS)-induced neuroinflammation via its pro-apoptotic action (Shen et al, 2015 ; Shi et al, 2015 ; Wu et al, 2016 ). It is well known that neuronal apoptosis is a major event in ischemic stroke, however, the role of Nrdp1 in ischemic neuronal death has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

Zhang

Yang

Wang

et al. 2017

Front. Cell. Neurosci.

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Neuregulin receptor degradation protein-1 (Nrdp1) is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12) cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD) treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO) and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8) in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

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“…Inhibition of specific tumour suppressor genes and activation of specific oncogenes have been demonstrated to be important for the occurrence and malignant progression of glioblastoma . STAT3 has been considered as a valuable therapeutic target in glioma because ( i ) multiple signalling pathways changed in glioma converge to STAT3 and ( ii ) it involves in multiple characteristics of glioma aggressiveness, via regulation of genes especially implicated in cell proliferation, growth, apoptosis, migration, invasion and neoangiogenesis .…”

Section: Discussionmentioning

confidence: 99%

Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling

Zhu

Zhang

Wang

et al. 2017

J Cellular Molecular Medi

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SH3GL2 (Src homology 3 (SH3) domain GRB2‐like 2) is mainly expressed in the central nervous system and regarded as a tumour suppressor in human glioma. However, the molecular mechanism of the SH3GL2 protein involved in malignant behaviours of human glioma has not been elucidated. In this study, we tried to investigate the role of SH3GL2 in glioma cell migration and invasion and explore its underlined molecular mechanism. Firstly, we discovered that the protein level of SH3GL2 was widely decreased in the human glioma patients, especially in high‐grade glioma tissues. Then, we determined the role of SH3GL2 in migration and invasion of glioma cells upon SH3GL2 knocking down and overexpressing. It was showed that knocking down of SH3GL2 promoted the migration and invasion of glioma cells, whereas overexpression of SH3GL2 inhibited them. Further study on molecular mechanism disclosed that silencing of SH3GL2 obviously activated the STAT3 (signal transducer and activator of transcription 3) signalling thereby promoting the expression and secretion of MMP2. On the contrary, overexpression of SH3GL2 had opposite effect. Taken together, the above results suggest that SH3GL2 suppresses migration and invasion behaviours of glioma cells through negatively regulating STAT3/MMP2 signalling and that loss of SH3GL2 may intensify the STAT3/MMP2 signalling thereby contributing to the migration and invasion of glioma cells.

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Nrdp1S, short variant of Nrdp1, inhibits human glioma progression by increasing Nrdp1‐mediated ErbB3 ubiquitination and degradation

Cited by 12 publications

References 28 publications

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling

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