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The expression change of OTUD3-PTEN signaling axis in glioma cells
Yi-Zhen Liu1, Xi-Xun Du1, Qi-Qi Zhao1
1Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.
Background:
OTU domain-containing protein 3 (OTUD3), as a deubiquitinase (DUB) belonging to the ovarian tumor protease (OTU) family, has been reported to suppress tumor via OTUD3-PTEN signaling axis. Glioma is the most common primary intracranial tumor with high invasiveness and poor prognosis. Although less than half of the patients have phosphatase and tension homologue deleted in chromosome 10 (PTEN) mutations or homozygous deletions, two-thirds of glioma possess diminished PTEN expression. Hence, it is conceivable that other obscure mechanisms may cause the decreased expression of the PTEN protein.
Methods:
OTUD3 expression was assessed in human normal and glioma tissues at The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/) and Genotype-Tissue Expression (GTEx) database (https://commonfund.nih.gov/GTex). The mRNA levels of OTUD3 in C6 cells and primary astrocytes were detected using real-time fluorescence quantitative PCR. Western blot was performed to assay PTEN and OTUD3 protein expression in C6 cells and primary astrocytes. By generating Kaplan-Meier curves, we predicted the association between OTUD3 expression and prognosis in glioma patients.
Results:
(I) OTUD3 transcription was markedly downregulated in glioma based on microarray data for gene expression between human gliomas and normal brain samples. (II) The mRNA levels of OTUD3 in C6 cells was significantly lower than that of in primary astrocytes. (III) The expressions of protein PTEN and OTUD3 in C6 cells were significantly decreased when compared with primary astrocytes. (IV) Glioma patients with high expression of OTUD3 had a longer survival time than patients with low expression.
Conclusions:
Our present findings demonstrated that low expression of OTUD3 in glioma may be involved in PTEN related glioma and may contribute to patient survival.
Insights
Low expression of OTU domain-containing protein 3 (OTUD3) is linked to glioma, potentially impacting PTEN protein levels and patient survival. Further research into OTUD3
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian tumor protease (OTU) domain-containing protein 3 (OTUD3) is a deubiquitinase (DUB) known to suppress tumors via the OTUD3-PTEN signaling pathway.
- Glioma, a prevalent and aggressive brain tumor, often exhibits diminished PTEN expression, even without PTEN gene mutations or deletions, suggesting other regulatory mechanisms.
- Understanding these mechanisms is crucial for improving glioma patient prognosis.
Purpose of the Study:
- To investigate the role of OTUD3 expression in glioma.
- To explore the relationship between OTUD3 and PTEN expression in glioma.
- To determine the prognostic significance of OTUD3 in glioma patients.
Main Methods:
- Assessed OTUD3 expression in human normal and glioma tissues using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases.
- Quantified OTUD3 mRNA levels in C6 glioma cells and primary astrocytes via real-time quantitative PCR.
- Evaluated PTEN and OTUD3 protein expression using Western blot and analyzed the association between OTUD3 expression and glioma patient survival using Kaplan-Meier curves.
Main Results:
- OTUD3 transcription was significantly downregulated in glioma tissues compared to normal brain samples.
- Both mRNA and protein levels of OTUD3 were markedly decreased in C6 glioma cells relative to primary astrocytes.
- Protein expression of PTEN was also significantly reduced in C6 cells compared to primary astrocytes.
- Higher OTUD3 expression in glioma patients correlated with longer survival times.
Conclusions:
- Low expression of OTUD3 is a characteristic of glioma and is associated with reduced PTEN levels.
- OTUD3 expression serves as a potential prognostic biomarker for glioma patients.
- These findings highlight OTUD3's involvement in PTEN-related glioma pathogenesis and its impact on patient outcomes.
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