The equilibrium of tumor suppression: DUBs as active regulators of PTEN

Christine, Audrey; Park, Mi Kyung; Song, Su Jung; Song, Min Sup

doi:10.1038/s12276-022-00887-w

Cited by 11 publications

(4 citation statements)

References 126 publications

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“…PTEN acts as a tumor suppressor and is frequently disrupted in several types of human cancers (Lee et al, 2018). Ubiquitination/deubiquitination is one of the major molecular mechanisms regulating protein stability, subcellular localization, and lipid phosphatase activity of PTEN (Christine et al, 2022;Wang et al, 2022a). As reported, OUT domain-containing protein 3 (OTUD3) remarkably upregulated the PTEN levels and suppressed tumorigenesis (Yuan et al, 2015).…”

Section: Discussionmentioning

confidence: 89%

UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

XIAO,

MA,

CHEN

et al. 2023

BIOCELL

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Background: Glioma is the most common primary brain tumor. Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can enhance the treatment efficacy. We previously demonstrated that the deubiquitinase biquitin carboxyl-terminal hydrolase L5 (UCHL5) was downregulated in human glioma. However, the effect and mechanism of UCHL5 on the proliferation of glioma cells remains unknown. Methods: Transfection of siRNA was used to knockdown the expression of UCHL5 in U251 cells. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Edu assay, and colony formation assay were employed to identify the effect of UCHL5 on the proliferation of U251 glioma cells. Western blotting and quantitative real-time PCR were carried out to detect the interaction of UCHL5 and PTEN. The effect of UCHL5 on the growth of glioma in vivo was evaluated in nude mice. Then Immunohistochemistry (IHC) were performed to analysis the expression of UCHL5 and PTEN in human glioma tissues. Results: Here, we have reported that silencing of UCHL5 could promote the proliferation of U251 glioma cells through MTT assay, Edu assay, and colony formation assay. Mechanically, we revealed that UCHL5 stabilizes the phosphatase and tensin homolog (PTEN) expression by deubiquitination, thereby inhibiting cell proliferation in U251 cells. Tumor xenograft experiments further demonstrated that silencing the UCHL5 expression could accelerate U251 cell growth in vivo. Finally, in human glioma tissue microarray, the positive correlation between UCHL5 and PTEN expression was confirmed through IHC assay. Conclusion: UCHL5 restrains the proliferation of U251 glioma cells by stabilizing and deubiquitinating PTEN. Our findings provide ideas for developing enhanced targeted PTEN therapy for patients with glioma.

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Section: Discussionmentioning

confidence: 89%

UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

XIAO,

MA,

CHEN

et al. 2023

BIOCELL

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“…6 E and G). The PTEN/AKT/GSK3β signaling, as a central anti-apoptotic intracellular signaling pathway, regulated cell growth, survival, proliferation, differentiation, and migration [ 29 , 30 ]. In brief, we demonstrate herein that SQLE affects the P53 signaling pathway and PTEN/AKT/GSK3β signaling pathway in BCa, which may be the key pathway for SQLE to regulate the progress of Bca.…”

Section: Resultsmentioning

confidence: 99%

SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53

Zou,

Chen,

Song

et al. 2023

Cancer Cell Int

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Bladder cancer (BCa) is one of the most common malignancies worldwide. However, the lack of accurate and effective targeted drugs has become a major problem in current clinical treatment of BCa. Studies have demonstrated that squalene epoxidase (SQLE), as a key rate-limiting enzyme in cholesterol biosynthesis, is involved in cancer development. In this study, our analysis of The Cancer Genome Atlas, The Genotype-Tissue Expression, and Gene Expression Omnibus databases showed that SQLE expression was significantly higher in cancer tissues than it was in adjacent normal tissues, and BCa tissues with a high SQLE expression displayed a poor prognosis. We then confirmed this result in qRT-PCR and immunohistochemical staining experiments, and our vitro studies demonstrated that SQLE knockdown inhibited tumor cell proliferation and metastasis through the PTEN/AKT/GSK3β signaling pathway. By means of rescue experiments, we proved that that P53 is a key molecule in SQLE-mediated regulation of the PTEN/AKT/GSK3β signaling pathway. Simultaneously, we verified the above findings through a tumorigenesis experiment in nude mice. In conclusion, our study shows that SQLE promotes BCa growth through the P53/PTEN/AKT/GSK3β axis, which may serve as a therapeutic biological target for BCa.

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“…PTEN Deficiency: The tumor suppressor gene PTEN, frequently lost or mutated in cancers, regulates the PI3K−AKT−mTOR signaling pathway. In mCRPC, PTEN gene deletion occurs in 40-60% of cases (22)(23)(24). Studies have shown that PTEN deficiency negatively impacts the effectiveness of abiraterone, but does not affect the antitumor activity of docetaxel (25,26).…”

Section: Discussionmentioning

confidence: 99%

Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review

Zhang,

Weng,

Zhu

et al. 2024

Front. Oncol.

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ObjectiveThis study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).MethodsWe systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs).ResultsSeven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m^2+prednisone (C20P) and cabazitaxel 25 mg/m^2+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs.ConclusionsBased on our network meta-analysis, we recommend cabazitaxel 20 mg/m^2+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.

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The equilibrium of tumor suppression: DUBs as active regulators of PTEN

Cited by 11 publications

References 126 publications

UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

SQLE Knockdown inhibits bladder cancer progression by regulating the PTEN/AKT/GSK3β signaling pathway through P53

Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review

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