scholarly journals TP53BP2 decreases cell proliferation and induces autophagy in neuroblastoma cell lines

2019 ◽  
Author(s):  
Yi Pang ◽  
Lianhong Pan ◽  
Yonghui Zhang ◽  
Guiyuan Liu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Lines

scholarly journals Itchy E3 ubiquitin-protein ligase promotes neuroblastoma progression in vitro and in vivo

2021 ◽  
Vol 3 (4) ◽  
pp. 12-24
Author(s):  
Mabao YUAN ◽  
Hanjiao HANG ◽  
Lubin YAN ◽  
Xuanjie HUANG ◽  
Ziyang SANG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Luciferase Reporter ◽  
Ubiquitin Protein Ligase ◽  
Neuroblastoma Cell Lines ◽  
Dual Luciferase Reporter Assay

[Objective] Neuroblastoma is the most common pediatric neuroendocrine tumor. Patients with high-risk neuroblastoma have poor clinical outcomes. Understanding the mechanisms underlying neuroblastoma progression could help identify potential therapeutic targets. This study aimed to explore the roles of itchy E3 ubiquitin-protein ligase (ITCH) in neuroblastoma progression using neuroblastoma cell lines and xenograft models of neuroblastoma. [Methods] ITCH-silencing or overexpressing neuroblastoma cells were established using two different human neuroblastoma cell lines, SK-N-AS and SH-SY5Y. In vitro and in vivo experiments were carried out to determine the effects of ITCH on neuroblastoma cell behaviors. The dual-luciferase reporter assay and co-transfection experiments were applied to determine the interaction of ITCH and miR-145-5p during neuroblastoma progression. [Results] In both cell lines, ITCH overexpression significantly promotes the proliferation, migration, and invasion capacities of neuroblastoma cells, while ITCH silencing with ShITCH suppressed neuroblastoma cell proliferation and induced apoptosis. Moreover, overexpression of ITCH decreased 51% and 54% the protein expressions of large tumor suppressor kinase 1 (LATS1), and inhibited 59% and 66% the phosphorylation of Yes-associated protein (YAP), concomitant with 2.02-fold and 2.56-fold increased expressions of cell proliferation marker Ki67 and 2.51-fold and 2.26-fold elevated levels of anti-apoptosis marker Bcl2 in SK-N-AS and SH-SY5Y cells, respectively. The dual-luciferase reporter assay demonstrated that ITCH interacted with miR-145-5p. Further in vitro and xenograft experiments showed that ITCH negatively affected the tumor-suppressive effect of miR-145-5p. [Conclusion] ITCH promotes neuroblastoma cell proliferation and metastasis by inhibiting LATS1 and promoting YAP nuclear translocation.

Downregulation of MSP58 suppresses cell proliferation in neuroblastoma cell lines

Neuroreport ◽  
2012 ◽  
Vol 23 (16) ◽  
pp. 932-936 ◽  
Author(s):  
Lin Wu ◽  
Zhi-guo Zhang ◽  
Huai-zhou Qin ◽  
Jian Zhang ◽  
Guo-dong Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Lines

scholarly journals TRIM59 knockdown inhibits cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Gang Chen ◽  
Weicheng Chen ◽  
Ming Ye ◽  
Weiqiang Tan ◽  
Bing Jia
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Annexin V ◽  
Cell Counting ◽  
Protein Levels ◽  
Proliferation And Apoptosis ◽  
Novel Biomarkers ◽  
Neuroblastoma Cell Lines

Abstract Neuroblastoma is the most common tumor in children, with a very poor prognosis. It is urgent to identify novel biomarkers to treat neuroblastoma, together with surgery, chemotherapy, and radiation. Human tripartite motif 59 (TRIM59), a member of the TRIM family, has been reported to participate in several human tumors. However, the exact role of TRIM59 in neuroblastoma is unknown. In the present study, real-time PCR and Western blot were used to measure mRNA and protein levels of TRIM59 in four neuroblastoma cell lines and in neuroblastoma tissues. Lentiviruses targeting TRIM59 were used to up/down-regulate TRIM59 expression levels. Cell Counting Kit-8 and Annexin-V/PI were used to analyze cell proliferation and apoptosis in neuroblastoma cell lines. Our data showed that TRIM59 knockdown inhibits cell proliferation while inducing apoptosis in SH-SY5Y and SK-N-SH neuroblastoma cell lines. TRIM59 knockdown up-regulated expression of Bax and Bim and down-regulated levels of Survivin, β-catenin, and c-myc. Interestingly, the inhibition of cell proliferation caused by TRIM59 knockdown could be blocked by LiCl, which is an agonist of Wnt/β-catenin signaling pathway. In contrast, TRIM59 overexpression could increase cell proliferation, up-regulate Survivin, β-catenin and c-myc, down-regulate Bax and Bim, and these effects could be blocked by XAV939, which is an inhibitor of Wnt/β-catenin signaling pathway. In addition, TRIM59 was up-regulated and positively related with β-catenin in neuroblastoma tissues. In conclusion, TRIM59 was up-regulated in neuroblastoma, and TRIM59 knockdown inhibited cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma.

Role of ALK activation in the development and maintenance of the neoplastic phenotype in neuroblastoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10008-10008
Author(s):  
M. Regairaz ◽  
F. Munier ◽  
H. Sartelet ◽  
V. Marty ◽  
M. Castaing ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Wild Type ◽  
Primary Tumors ◽  
Normal Tissues ◽  
Anaplastic Lymphoma ◽  
Neuroblastoma Cell Lines

10008 Background: Activating mutations of the Anaplastic Lymphoma Kinase (ALK) receptor could be responsible for most familial neuroblastoma cases and for up to 15% of somatic cases. The objective of the present study was to further investigate the role of ALK activation in neuroblastoma. Methods: Tissue microarrays were constructed containing 101 primary tumors and 56 paired normal tissues. Sections were immunostained with anti-ALK or anti-P-ALK antibodies, and with antibodies directed against the ALK ligands: PTN (Pleiotrophin) or MDK (Midkine). The Wilcoxon signed rank test was applied for comparison of paired data. Associations with prognostic factors were analyzed using t-tests. Effects of the ALK inhibitor TAE684 (Novartis) on cell proliferation and signaling was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. Results: ALK was expressed in about 100% of tumors and normal tissues, while phospho-ALK was detected in 5% of normal tissues and 50% of tumors. Sequencing of the kinase domain of ALK showed that its phosphorylation was largely independent of mutations and we found that MDK and PTN ligands were expressed in 66% and 50% of tumors, respectively. Interestingly, ALK, P-ALK, and MDK were expressed at higher levels in tumors as compared with paired normal tissues (p < 0.0001), while PTN showed an inverse tendency, being more expressed in normal tissues (p = 0.07). In tumors, P-ALK was associated with good-prognosis factors, including favorable stages (p = 0.01), absence of MYCN amplification (p = 0.05) and a younger age at diagnosis (p = 0.03). Inhibition of cell proliferation by TAE684 was detectible in all neuroblastoma cell lines, regardless of ALK status. However, TAE684 failed to demonstrate antitumor activity in advanced stage neuroblastoma xenografts expressing either a wild-type or a mutated ALK. Interestingly, ALK pathway activation (P-STAT3, P-AKT) was weak or barely detectible in these xenografts. Conclusions: ALK activation occurs during neuroblastoma oncogenesis, along with a concomitant switch between the expressions of PTN and MDK. However, ALK may not be a relevant therapeutic target since in vivo inhibition showed no antitumor activity. [Table: see text]

The DNA-binding protein YB-1 is a direct MYCN target and influences repair and resistance in neuroblastoma cell lines

2010 ◽  
Vol 222 (03) ◽  
Author(s):  
S Degen ◽  
S Kuhfittig-Kulle ◽  
JH Schulte ◽  
F Westermann ◽  
A Schramm ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Lines ◽  
Binding Protein ◽  
Neuroblastoma Cell ◽  
Dna Binding Protein ◽  
Neuroblastoma Cell Lines

Negative and positive effects of an IAP-LTR on nearby Pcdaα gene expression in the central nervous system and neuroblastoma cell lines

Gene ◽  
2004 ◽  
Vol 337 ◽  
pp. 91-103 ◽  
Author(s):  
Hidehiko Sugino ◽  
Tomoko Toyama ◽  
Yusuke Taguchi ◽  
Shigeyuki Esumi ◽  
Mitsuhiro Miyazaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Positive Effects ◽  
The Central Nervous System ◽  
Neuroblastoma Cell Lines

scholarly journals The Anti-Tumor Activity of the NEDD8 Inhibitor Pevonedistat in Neuroblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6565
Author(s):  
Jennifer H. Foster ◽  
Eveline Barbieri ◽  
Linna Zhang ◽  
Kathleen A. Scorsone ◽  
Myrthala Moreno-Smith ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Wild Type ◽  
Tumor Weight ◽  
Cycle Arrest ◽  
P53 Status ◽  
Neuroblastoma Cell Lines ◽  
Anti Tumor Activity

Pevonedistat is a neddylation inhibitor that blocks proteasomal degradation of cullin–RING ligase (CRL) proteins involved in the degradation of short-lived regulatory proteins, including those involved with cell-cycle regulation. We determined the sensitivity and mechanism of action of pevonedistat cytotoxicity in neuroblastoma. Pevonedistat cytotoxicity was assessed using cell viability assays and apoptosis. We examined mechanisms of action using flow cytometry, bromodeoxyuridine (BrDU) and immunoblots. Orthotopic mouse xenografts of human neuroblastoma were generated to assess in vivo anti-tumor activity. Neuroblastoma cell lines were very sensitive to pevonedistat (IC50 136–400 nM). The mechanism of pevonedistat cytotoxicity depended on p53 status. Neuroblastoma cells with mutant (p53MUT) or reduced levels of wild-type p53 (p53si-p53) underwent G2-M cell-cycle arrest with rereplication, whereas p53 wild-type (p53WT) cell lines underwent G0-G1 cell-cycle arrest and apoptosis. In orthotopic neuroblastoma models, pevonedistat decreased tumor weight independent of p53 status. Control mice had an average tumor weight of 1.6 mg + 0.8 mg versus 0.5 mg + 0.4 mg (p < 0.05) in mice treated with pevonedistat. The mechanism of action of pevonedistat in neuroblastoma cell lines in vitro appears p53 dependent. However, in vivo studies using mouse neuroblastoma orthotopic models showed a significant decrease in tumor weight following pevonedistat treatment independent of the p53 status. Novel chemotherapy agents, such as the NEDD8-activating enzyme (NAE) inhibitor pevonedistat, deserve further study in the treatment of neuroblastoma.

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